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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__197882128967036__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__197882128967036__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI%3ACHEBI%3A17154","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__197882128967036__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"197882128967036","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__197882128967036__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 10180713443D starting HoverWatcher_5 Time for openFile( Marvin 10180713443D 15 15 0 0 1 0 999 V2000 -2.1376 1.1964 0.1234 C 0 0 0 0 0 0 0 0 0 6 0 0 -2.1864 -0.2078 0.1471 C 0 0 0 0 0 0 0 0 0 5 0 0 -0.9762 -0.9258 0.1433 C 0 0 0 0 0 0 0 0 0 4 0 0 0.2409 1.1546 0.0875 C 0 0 0 0 0 0 0 0 0 2 0 0 -0.9377 1.8242 0.0967 N 0 0 0 0 0 0 0 0 0 1 0 0 0.2761 -0.2629 0.1061 C 0 0 0 0 0 0 0 0 0 3 0 0 1.4741 -0.9653 0.0791 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5863 -2.0791 0.5707 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5285 -0.4944 -0.4818 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.9947 1.7508 0.1257 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0845 -0.6955 0.1635 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0290 -1.9482 0.1542 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0955 1.7154 0.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3284 -0.9777 -0.4810 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4936 0.3375 -0.9077 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 4 0 0 0 0 3 2 4 0 0 0 0 1 5 4 0 0 0 0 5 4 4 0 0 0 0 4 6 4 0 0 0 0 3 6 4 0 0 0 0 6 7 1 0 0 0 0 7 9 1 0 0 0 0 7 8 2 0 0 0 0 1 10 1 0 0 0 0 2 11 1 0 0 0 0 3 12 1 0 0 0 0 4 13 1 0 0 0 0 9 14 1 0 0 0 0 9 15 1 0 0 0 0 M END): 16 ms reading 15 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 15 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| Nicotinamide (INN, BAN UK) or niacinamide (USAN US) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used orally (swallowed by mouth) to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, nicotinamide has the benefit of not causing skin flushing. As a cream, it is used to treat acne, and has been observed in clinical studies to improve the appearance of aging skin by reducing hyperpigmentation and redness. It is a water-soluble vitamin.
Side effects are minimal. At high doses, liver problems may occur. Normal amounts are safe for use during pregnancy. Nicotinamide is in the vitamin B family of medications, specifically the vitamin B3 complex. It is an amide of nicotinic acid. Foods that contain nicotinamide include yeast, meat, milk, and green vegetables.
Nicotinamide was discovered between 1935 and 1937. It is on the World Health Organization's List of Essential Medicines. Nicotinamide is available as a generic medication and over the counter. Commercially, nicotinamide is made from either nicotinic acid (niacin) or nicotinonitrile. In some countries, grains have nicotinamide added to them.
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Read full article at Wikipedia
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| InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9) |
| DFPAKSUCGFBDDF-UHFFFAOYSA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
urine
(BTO:0001419).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
breast milk
(ENVO:02000031).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
|
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Homo sapiens
(NCBI:txid9606)
|
From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
|
From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
|
From MetaboLights
See:
MetaboLights Study
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|
Homo sapiens
(NCBI:txid9606)
|
From MetaboLights
See:
MetaboLights Study
|
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Homo sapiens
(NCBI:txid9606)
|
From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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From MetaboLights
See:
MetaboLights Study
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
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metabolite
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
(via alkaloid )
Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
EC 3.5.1.98 (histone deacetylase) inhibitor
An EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the function of histone deacetylase (EC 3.5.1.98).
Sir2 inhibitor
An EC 3.5.1.98 (histone deacetylase) inhibitor that interferes with the action of Sir2.
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
An EC 2.4.2.* (pentosyltransferase) inhibitor that interferes with the action of a NAD+ ADP-ribosyltransferase (EC 2.4.2.30).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
human urinary metabolite
Any metabolite (endogenous or exogenous) found in human urine samples.
cofactor
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
water-soluble vitamin (role)
Any vitamin that dissolves in water and readily absorbed into tissues for immediate use. Unlike the fat-soluble vitamins, they are not stored in the body and need to be replenished regularly in the diet and will rarely accumulate to toxic levels since they are quickly excreted from the body via urine.
(via B vitamin )
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neuroprotective agent
Any compound that can be used for the treatment of neurodegenerative disorders.
anti-inflammatory agent
Any compound that has anti-inflammatory effects.
geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
(via B vitamin )
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View more via ChEBI Ontology
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Outgoing
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nicotinamide
(CHEBI:17154)
has functional parent
nicotinic acid
(CHEBI:15940)
nicotinamide
(CHEBI:17154)
has role
Escherichia coli metabolite
(CHEBI:76971)
nicotinamide
(CHEBI:17154)
has role
Saccharomyces cerevisiae metabolite
(CHEBI:75772)
nicotinamide
(CHEBI:17154)
has role
anti-inflammatory agent
(CHEBI:67079)
nicotinamide
(CHEBI:17154)
has role
antioxidant
(CHEBI:22586)
nicotinamide
(CHEBI:17154)
has role
cofactor
(CHEBI:23357)
nicotinamide
(CHEBI:17154)
has role
EC 2.4.2.30 (NAD+ ADP-ribosyltransferase) inhibitor
(CHEBI:62913)
nicotinamide
(CHEBI:17154)
has role
EC 3.5.1.98 (histone deacetylase) inhibitor
(CHEBI:61115)
nicotinamide
(CHEBI:17154)
has role
geroprotector
(CHEBI:176497)
nicotinamide
(CHEBI:17154)
has role
human urinary metabolite
(CHEBI:84087)
nicotinamide
(CHEBI:17154)
has role
metabolite
(CHEBI:25212)
nicotinamide
(CHEBI:17154)
has role
mouse metabolite
(CHEBI:75771)
nicotinamide
(CHEBI:17154)
has role
neuroprotective agent
(CHEBI:63726)
nicotinamide
(CHEBI:17154)
has role
Sir2 inhibitor
(CHEBI:71181)
nicotinamide
(CHEBI:17154)
is a
pyridine alkaloid
(CHEBI:26416)
nicotinamide
(CHEBI:17154)
is a
pyridinecarboxamide
(CHEBI:25529)
nicotinamide
(CHEBI:17154)
is a
vitamin B3
(CHEBI:176839)
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Incoming
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1-[(2-chlorophenyl)methyl]-2-oxo-6-(trifluoromethyl)-3-pyridinecarboxamide
(CHEBI:114321)
has functional parent
nicotinamide
(CHEBI:17154)
1-[[oxo(3-pyridinyl)methyl]amino]-3-(4-propan-2-ylphenyl)thiourea
(CHEBI:120875)
has functional parent
nicotinamide
(CHEBI:17154)
1-methylnicotinamide
(CHEBI:16797)
has functional parent
nicotinamide
(CHEBI:17154)
2-(2,4-dimethylanilino)-N-(thiophen-2-ylmethyl)-3-pyridinecarboxamide
(CHEBI:104887)
has functional parent
nicotinamide
(CHEBI:17154)
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-3-pyridinecarboxamide
(CHEBI:91424)
has functional parent
nicotinamide
(CHEBI:17154)
2-(4-chloro-2-methylanilino)-3-pyridinecarboxamide
(CHEBI:108168)
has functional parent
nicotinamide
(CHEBI:17154)
2-(methylthio)nicotinamide
(CHEBI:228655)
has functional parent
nicotinamide
(CHEBI:17154)
2-methylnicotinamide
(CHEBI:68440)
has functional parent
nicotinamide
(CHEBI:17154)
2-oxo-N-(2-thiazolyl)-1H-pyridine-3-carboxamide
(CHEBI:120549)
has functional parent
nicotinamide
(CHEBI:17154)
5-bromo-N-(4-methyl-2-thiazolyl)-3-pyridinecarboxamide
(CHEBI:122191)
has functional parent
nicotinamide
(CHEBI:17154)
5-bromo-N-[(2-pyridinylamino)-sulfanylidenemethyl]-3-pyridinecarboxamide
(CHEBI:120534)
has functional parent
nicotinamide
(CHEBI:17154)
5-bromo-N-[(5-nitro-2-thiophenyl)methylideneamino]-3-pyridinecarboxamide
(CHEBI:104973)
has functional parent
nicotinamide
(CHEBI:17154)
5-bromo-N-[[(3-methyl-2-pyridinyl)amino]-sulfanylidenemethyl]-3-pyridinecarboxamide
(CHEBI:93987)
has functional parent
nicotinamide
(CHEBI:17154)
5-bromo-N-[[(4-methyl-2-pyridinyl)amino]-sulfanylidenemethyl]-3-pyridinecarboxamide
(CHEBI:116399)
has functional parent
nicotinamide
(CHEBI:17154)
5-hydroxy-N-[2-[[(5-hydroxy-3-pyridinyl)-oxomethyl]amino]propyl]-3-pyridinecarboxamide
(CHEBI:104006)
has functional parent
nicotinamide
(CHEBI:17154)
6-methoxy-4-(trifluoromethyl)nicotinamide
(CHEBI:183364)
has functional parent
nicotinamide
(CHEBI:17154)
6-methyl-N-(2-pyridinylmethylideneamino)-3-pyridinecarboxamide
(CHEBI:107154)
has functional parent
nicotinamide
(CHEBI:17154)
6-methyl-N-[(2-methyl-3-phenylprop-2-enylidene)amino]-3-pyridinecarboxamide
(CHEBI:105981)
has functional parent
nicotinamide
(CHEBI:17154)
6-Methylnicotinamide
(CHEBI:88954)
has functional parent
nicotinamide
(CHEBI:17154)
N-glycosylnicotinamide
(CHEBI:25526)
has functional parent
nicotinamide
(CHEBI:17154)
N-methylnicotinamide
(CHEBI:64399)
has functional parent
nicotinamide
(CHEBI:17154)
N-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}nicotinamide
(CHEBI:39634)
has functional parent
nicotinamide
(CHEBI:17154)
acetic acid 2-[[oxo(3-pyridinyl)methyl]amino]ethyl ester
(CHEBI:92313)
has functional parent
nicotinamide
(CHEBI:17154)
flumetnicam
(CHEBI:231554)
has functional parent
nicotinamide
(CHEBI:17154)
Himeic acid G
(CHEBI:211171)
has functional parent
nicotinamide
(CHEBI:17154)
hydroxymethylnicotinamide
(CHEBI:134775)
has functional parent
nicotinamide
(CHEBI:17154)
Myxochelin N
(CHEBI:222142)
has functional parent
nicotinamide
(CHEBI:17154)
Myxochelin O
(CHEBI:222138)
has functional parent
nicotinamide
(CHEBI:17154)
N'3-(3,4,5-trimethoxybenzylidene)pyridine-3-carbohydrazide
(CHEBI:183773)
has functional parent
nicotinamide
(CHEBI:17154)
N,N-Dihexylnicotinamide
(CHEBI:189375)
has functional parent
nicotinamide
(CHEBI:17154)
N-(1-adamantyl)-5-hydroxy-3-pyridinecarboxamide
(CHEBI:104155)
has functional parent
nicotinamide
(CHEBI:17154)
N-(2-fluorophenyl)-2-methyl-6-(trifluoromethyl)nicotinamide
(CHEBI:189499)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2-methyl-3-phenylprop-2-enylidene)amino]-3-pyridinecarboxamide
(CHEBI:105703)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[2-(1-piperidinyl)ethylamino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:100861)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118385)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118398)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6R)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118597)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[2-(1-piperidinyl)ethylamino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:101057)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118291)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118425)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[2-(1-piperidinyl)ethylamino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:99262)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118445)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6R)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118736)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[2-(1-piperidinyl)ethylamino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:100693)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124890)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124301)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2R,3S,6S)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118714)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[2-(1-piperidinyl)ethylamino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:102693)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124865)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124262)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6R)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118717)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-(2-piperidin-1-ylethylamino)ethyl]-3,6-dihydro-2H-pyran-3-yl]pyridine-3-carboxamide
(CHEBI:98207)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124899)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:124859)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3R,6S)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118547)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6R)-2-(hydroxymethyl)-6-[2-oxo-2-(2-piperidin-1-ylethylamino)ethyl]-3,6-dihydro-2H-pyran-3-yl]pyridine-3-carboxamide
(CHEBI:98467)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118474)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6R)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118386)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6R)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118573)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-(2-piperidin-1-ylethylamino)ethyl]-3,6-dihydro-2H-pyran-3-yl]pyridine-3-carboxamide
(CHEBI:97296)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118300)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6S)-2-(hydroxymethyl)-6-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethyl]-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118418)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(2S,3S,6S)-6-[2-[(3,4-dichlorophenyl)methylamino]-2-oxoethyl]-2-(hydroxymethyl)-3,6-dihydro-2H-pyran-3-yl]-3-pyridinecarboxamide
(CHEBI:118748)
has functional parent
nicotinamide
(CHEBI:17154)
N-[(3,3-dimethyl-5-oxocyclohexylidene)amino]-3-pyridinecarboxamide
(CHEBI:108969)
has functional parent
nicotinamide
(CHEBI:17154)
N-[1,1,1,3,3,3-hexafluoro-2-(2-pyridinylmethylamino)propan-2-yl]-3-pyridinecarboxamide
(CHEBI:94517)
has functional parent
nicotinamide
(CHEBI:17154)
N-[2-[2-[2-[[oxo(3-pyridinyl)methyl]amino]ethoxy]ethoxy]ethyl]-3-pyridinecarboxamide
(CHEBI:114454)
has functional parent
nicotinamide
(CHEBI:17154)
N-[5-(2-chlorophenyl)-1,3,4-oxadiazol-2-yl]-3-pyridinecarboxamide
(CHEBI:107956)
has functional parent
nicotinamide
(CHEBI:17154)
N-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]-3-pyridinecarboxamide
(CHEBI:105309)
has functional parent
nicotinamide
(CHEBI:17154)
N-[6-(1-oxopentylamino)-3-pyridinyl]-3-pyridinecarboxamide
(CHEBI:121625)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2R,3R)-5-[(2R)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95855)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2R,3R)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96617)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2R,3S)-5-[(2R)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95777)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2R,3S)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95921)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2S,3R)-5-[(2R)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96139)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2S,3R)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95864)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2S,3S)-5-[(2R)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96344)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(2S,3S)-5-[(2S)-1-hydroxypropan-2-yl]-3-methyl-8-(3-methylbut-1-ynyl)-6-oxo-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-2-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95684)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5R)-2-[(2R)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95995)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5R)-2-[(2S)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95600)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5R)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2R)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95717)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5R)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2S)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95552)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5S)-2-[(2R)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95670)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5S)-2-[(2S)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96381)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5S)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2R)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96468)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4R,5S)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2S)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95700)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5R)-2-[(2R)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95969)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5R)-2-[(2S)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96539)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5R)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2R)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95912)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5R)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2S)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:116657)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5R)-8-bromo-2-[(2S)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:110094)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5S)-2-[(2R)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:95974)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5S)-2-[(2S)-1-hydroxypropan-2-yl]-8-(2-methoxyphenyl)-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96360)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5S)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2R)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96511)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[(4S,5S)-8-[2-(1-hydroxycyclopentyl)ethynyl]-2-[(2S)-1-hydroxypropan-2-yl]-4-methyl-1,1-dioxo-4,5-dihydro-3H-6,1$l^{6},2-benzoxathiazocin-5-yl]methyl]-N-methyl-3-pyridinecarboxamide
(CHEBI:96067)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[3-methoxy-4-[2-(4-methylanilino)-2-oxoethoxy]phenyl]methylideneamino]-3-pyridinecarboxamide
(CHEBI:116480)
has functional parent
nicotinamide
(CHEBI:17154)
N-[[5-(4-nitrophenyl)-2-furanyl]methylideneamino]-3-pyridinecarboxamide
(CHEBI:116670)
has functional parent
nicotinamide
(CHEBI:17154)
N-methyl-N-[5-(3-pyridinyl)-1,3,4-thiadiazol-2-yl]-3-pyridinecarboxamide
(CHEBI:115102)
has functional parent
nicotinamide
(CHEBI:17154)
nicorandil
(CHEBI:31905)
has functional parent
nicotinamide
(CHEBI:17154)
Nicoxamat
(CHEBI:173404)
has functional parent
nicotinamide
(CHEBI:17154)
nikethamide
(CHEBI:134814)
has functional parent
nicotinamide
(CHEBI:17154)
Penipyridone A
(CHEBI:227809)
has functional parent
nicotinamide
(CHEBI:17154)
Penipyridone C
(CHEBI:227819)
has functional parent
nicotinamide
(CHEBI:17154)
Penipyridone D
(CHEBI:227822)
has functional parent
nicotinamide
(CHEBI:17154)
Penipyridone F
(CHEBI:227832)
has functional parent
nicotinamide
(CHEBI:17154)
Pestalamide C
(CHEBI:197575)
has functional parent
nicotinamide
(CHEBI:17154)
Pestalamide D
(CHEBI:215530)
has functional parent
nicotinamide
(CHEBI:17154)
Poronitin B
(CHEBI:202835)
has functional parent
nicotinamide
(CHEBI:17154)
|
nicotinamida
|
WHO MedNet
|
|
nicotinamide
|
WHO MedNet
|
nicotinamide
|
WHO MedNet
|
nicotinamidum
|
WHO MedNet
|
|
3-carbamoylpyridine
|
ChemIDplus
|
|
3-pyridinecarboxamide
|
NIST Chemistry WebBook
|
|
β-pyridinecarboxamide
|
ChemIDplus
|
|
β-pyridinecarboxamide
|
NIST Chemistry WebBook
|
|
m-(aminocarbonyl)pyridine
|
ChemIDplus
|
|
niacin
|
ChEBI
|
|
Niacinamide
|
KEGG COMPOUND
|
|
niamide
|
ChemIDplus
|
Nicotinamid
|
ChEBI
|
|
nicotinamide
|
UniProt
|
|
nicotine acid amide
|
ChemIDplus
|
|
nicotine amide
|
ChemIDplus
|
|
nicotinic acid amide
|
ChemIDplus
|
|
nicotinic amide
|
ChemIDplus
|
|
Nicotinsäureamid
|
ChEBI
|
|
nicotylamide
|
ChemIDplus
|
|
Nikotinamid
|
ChemIDplus
|
|
Nikotinsäureamid
|
ChEBI
|
|
pyridine-3-carboxylic acid amide
|
ChemIDplus
|
vitamin B3
 Note: (2015-01-13) Note that the term 'vitamin B3' has also been used as a synonym for nicotinic acid, as well as for other molecules that exhibit the biological activity of nicotinic acid. |
|
ChemIDplus
|
Vitamin PP
| Note: (2015-01-13) Note that the term 'vitamin PP' has also been used as a synonym for nicotinic acid. |
|
KEGG COMPOUND
|
|
3336
|
Gmelin Registry Number
|
Gmelin
|
|
383619
|
Reaxys Registry Number
|
Reaxys
|
|
98-92-0
|
CAS Registry Number
|
ChemIDplus
|
|
98-92-0
|
CAS Registry Number
|
NIST Chemistry WebBook
|
Deordieva E, Shvets O, Voronin K, Maschan A, Welte K, Skokowa J, Novichkova G, Shcherbina A (2021)
Nicotinamide (vitamin B3) treatment improves response to G-CSF in severe congenital neutropenia patients.
British journal of haematology 192, 788-792 [PubMed:33471934] | Horimatsu T, Blomkalns AL, Ogbi M, Moses M, Kim D, Patel S, Gilreath N, Reid L, Benson TW, Pye J, Ahmadieh S, Thompson A, Robbins N, Mann A, Edgell A, Benjamin S, Stansfield BK, Huo Y, Fulton DJ, Agarwal G, Singh N, Offermanns S, Weintraub NL, Kim HW (2020)
Niacin protects against abdominal aortic aneurysm formation via GPR109A independent mechanisms: role of NAD+/nicotinamide.
Cardiovascular research 116, 2226-2238 [PubMed:31710686]
[show Abstract]
AimsChronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation.Methods and resultsMice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation.ConclusionNiacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA. | Crunkhorn S (2020)
Fighting glioblastoma with vitamin B3.
Nature reviews. Drug discovery 19, 310 [PubMed:32249824] | Huber R, Wong A (2020)
Nicotinamide: An Update and Review of Safety & Differences from Niacin.
Skin therapy letter 25, 7-11 [PubMed:33196157]
[show Abstract]
Nicotinamide (or niacinamide), a form of vitamin B3 that is often confused with its precursor nicotinic acid (or niacin), is a low-cost, evidence-based oral treatment option for actinic keratosis, squamous cell carcinomas, basal cell carcinomas, and bullous pemphigoid. Despite its favorable safety profile and affordability, the integration of nicotinamide into clinical practice is an ongoing process, and like many over-the-counter supplements it has faced some barriers. The purpose of this article is to address some of those barriers by reviewing its efficacy, safety profile, and emphasizing the difference between nicotinamide and niacin. Lastly, we offer practical guidance around recommendations and the availability of nicotinamide, which can be hard to find for patients and providers alike. | Kim B, Halliday GM, Damian DL (2015)
Oral nicotinamide and actinic keratosis: a supplement success story.
Current problems in dermatology 46, 143-149 [PubMed:25561219]
[show Abstract]
Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions. Recent studies have shown that nicotinamide, in both oral and topical forms, is able to prevent ultraviolet-induced immunosuppression in humans [1,2,3] and mice [4,5]. Immunosuppression is a known factor for the progression of premalignant lesions, such as actinic keratosis [6]. Murine studies have shown that nicotinamide is also able to protect against photocarcinogenesis [4,5]. Preliminary human studies suggest that nicotinamide may help prevent skin cancers and enhance the regression of actinic keratoses. | Rennie G, Chen AC, Dhillon H, Vardy J, Damian DL (2015)
Nicotinamide and neurocognitive function.
Nutritional neuroscience 18, 193-200 [PubMed:24559077]
[show Abstract]
Nicotinamide, or vitamin B3, is a precursor of nicotinamide adenine dinucleotide (NAD(+)) and is involved in a multitude of intra- and inter-cellular processes, which regulate some of the cell's metabolic, stress, and immune responses to physiological or pathological signals. As a precursor of NAD(+), which is a key coenzyme in the production of adenosine triphosphate or cellular energy, nicotinamide has been investigated for potential neuroprotective effects in cellular, animal, and human studies. Objectives We aimed to summarize the current evidence on the effect of dietary and supplemental nicotinamide on cognitive function. Methods A literature review was conducted on the effects of nicotinamide and its derivatives as a preventive and therapeutic agent for disorders of neurocognitive function. Specific conditions examined include age-related cognitive decline, Alzheimer's disease, Parkinson's disease, and ischaemic and traumatic brain injury. Results Data from animal and human interventional studies and epidemiological research suggests that nicotinamide may be beneficial in preserving and enhancing neurocognitive function. Discussion Nicotinamide is non-toxic, inexpensive and widely available, and interventional studies in humans, using supplemental doses of nicotinamide, are now warranted. | Domínguez-Gómez G, Díaz-Chávez J, Chávez-Blanco A, Gonzalez-Fierro A, Jiménez-Salazar JE, Damián-Matsumura P, Gómez-Quiroz LE, Dueñas-González A (2015)
Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin.
Oncology reports 33, 721-728 [PubMed:25504347]
[show Abstract]
Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1‑ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1‑deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild‑type MDA-MB-231 cells, to demonstrate its effects as a chemo‑ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo‑ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo‑ or radiosensitizing agent regardless of the BRCA1 status in breast cancer. | Chen AC, Damian DL (2014)
Nicotinamide and the skin.
The Australasian journal of dermatology 55, 169-175 [PubMed:24635573]
[show Abstract]
Nicotinamide, an amide form of vitamin B3, boosts cellular energy and regulates poly-ADP-ribose-polymerase 1, an enzyme with important roles in DNA repair and the expression of inflammatory cytokines. Nicotinamide shows promise for the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. In particular, recent studies have also shown it to be a potential agent for reducing actinic keratoses and preventing skin cancers. | Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, Heiland I, Birringer M, Groth M, Segref A, Kanfi Y, Price NL, Schmeisser S, Schuster S, Pfeiffer AF, Guthke R, Platzer M, Hoppe T, Cohen HY, Zarse K, Sinclair DA, Ristow M (2013)
Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.
Nature chemical biology 9, 693-700 [PubMed:24077178]
[show Abstract]
Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan. In contrast with recent observations, here we find that overexpression of sir-2.1, the ortholog of mammalian SirT1, does extend Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir-2.1. We identify a previously unknown C. elegans nicotinamide-N-methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM. Disruption and overexpression of anmt-1 have opposing effects on lifespan independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated lifespan extension. MNA serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic reactive oxygen species signal to promote C. elegans longevity. Taken together, sirtuin-mediated lifespan extension depends on methylation of NAM, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation. | Smilowitz JT, O'Sullivan A, Barile D, German JB, Lönnerdal B, Slupsky CM (2013)
The human milk metabolome reveals diverse oligosaccharide profiles.
The Journal of nutrition 143, 1709-1718 [PubMed:24027187]
[show Abstract]
Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (<20%), including lactose, urea, glutamate, myo-inositol, and creatinine. Principal components analysis identified 2 clear groups of participants who were differentiable on the basis of milk oligosaccharide concentration and who were classified as secretors or nonsecretors of fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'-fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of the interrelations between the milk sugars by using Spearman rank correlations revealed significant positive and negative associations, including positive correlations between fucose and products of the FUT2 gene and negative correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene. The total concentration of milk oligosaccharides was conserved among participants (%CV = 18%), suggesting tight regulation of total oligosaccharide production; however, concentrations of specific oligosaccharides varied widely between participants (%CV = 30.4-84.3%). The variability in certain milk metabolites suggests possible roles in infant or infant gut microbial development. This trial was registered at clinicaltrials.gov as NCT01817127. | Koh PO (2013)
Nicotinamide restores the reduction of parvalbumin in cerebral ischemic injury.
The Journal of veterinary medical science 75, 225-229 [PubMed:23047329]
[show Abstract]
The aim of this study investigated whether nicotinamide affects parvalbumin expression in focal cerebral ischemic injury. Rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after middle cerebral artery occlusion (MCAO), and cerebral cortex tissues were collected 24 hr after MCAO. Nicotinamide significantly decreases the volume of infarct areas in the cerebral cortex. A proteomic approach revealed that MCAO induces decreases of parvalbumin levels, while nicotinamide treatment prevents injury-induced decreases in parvalbumin. RT-PCR and Western blot analyses demonstrated that nicotinamide restores injury-induced decreases in parvalbumin. Moreover, immunohistochemical staining confirmed that the numbers of parvalbumin-positive cells were decreased in vehicle-treated animals with MCAO, and that nicotinamide averted this decrease. In cultured hippocampal cells, nicotinamide treatment prevents the glutamate exposure-induced increase in intracellular Ca(2+) concentration and decrease in parvalbumin expression. These results suggest the fact that the maintenance of parvalbumin expression is mediated to the neuroprotective function of nicotinamide against ischemic brain injury. | Sowa M, Ślepokura K, Matczak-Jon E (2012)
A 1:1 cocrystal of baicalein with nicotinamide.
Acta crystallographica. Section C, Crystal structure communications 68, o262-5 [PubMed:22763693]
[show Abstract]
Cocrystallization of baicalein with nicotinamide yields a 1:1 cocrystal [systematic name: pyridine-3-carboxamide-5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one (1/1)], C(6)H(6)N(2)O·C(15)H(10)O(5). The asymmetric unit contains one baicalein and one nicotinamide molecule, both in neutral forms. Molecules in the cocrystal form column motifs stabilized by an array of intermolecular hydrogen bonds. | Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D, Azevedo WF (2012)
Anti-Trypanosoma cruzi activity of nicotinamide.
Acta tropica 122, 224-229 [PubMed:22281243]
[show Abstract]
Inhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in the vacuolization in the cytoplasm were observed in epimastigotes treated with nicotinamide. Analysis of the complex of Sir2 and nicotinamide revealed the details of the possible ligand-target interaction. Our data reveal a potential use of TcSir2 as a target for anti-T. cruzi drug discovery. | Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012)
Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer.
Analytical chemistry 84, 6429-6437 [PubMed:22770225]
[show Abstract]
Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Shibata K, Imai E, Sano M, Fukuwatari T (2012)
The urinary excretory ratio of nicotinamide catabolites was associated with the conversion ratio of tryptophan to nicotinamide in growing rats fed a niacin-free 20% casein diet.
Bioscience, biotechnology, and biochemistry 76, 186-188 [PubMed:22232263]
[show Abstract]
Weaning rats were fed a niacin-free 20% casein diet. Twenty-four-h-urine samples were collected, and nicotinamide and its catabolites were measured. A correlation was found between the urinary excretory ratio of nicotinamide catabolites (N(1)-methyl-2-pyridone-5-carboxamide + N(1)-methyl-4-pyridone-3-carboxamide)/N(1)-methylnicotinamide and the tryptophan-nicotinamide conversion ratio during growing period of the rats. This indicates the possibility that the conversion ratio can be deduced from the excretory ratio. | Zhao Y, Qi L, Chen F, Chen F, Dong Y, Kong Y, Wu Y, Fan C (2012)
Ultrasensitive and selective detection of nicotinamide adenine dinucleotide by target-triggered ligation-rolling circle amplification.
Chemical communications (Cambridge, England) 48, 3354-3356 [PubMed:22361740]
[show Abstract]
An ultrasensitive fluorescence assay for nicotinamide adenine dinucleotide (NAD(+)) was developed by target-triggered ligation-rolling circle amplification (L-RCA). This novel approach can detect as low as 1 pM NAD(+), much lower than those of previously reported biosensors, and exhibits high discrimination ability even against 200 times excess of NAD(+) analogs. | Zhao J, Zhang L, Jiang J, Shen G, Yu R (2012)
A label-free fluorescence DNA probe based on ligation reaction with quadruplex formation for highly sensitive and selective detection of nicotinamide adenine dinucleotide.
Chemical communications (Cambridge, England) 48, 4468-4470 [PubMed:22456321]
[show Abstract]
A simple label-free fluorescent sensing scheme for sensitive and selective detection of nicotinamide adenine dinucleotide (NAD(+)) has been developed based on DNA ligation reaction with ligand-responsive quadruplex formation. This approach can detect 0.5 nM NAD(+) with high selectivity against other NAD(+) analogs. | Chen TY, Lin MH, Lee WT, Huang SY, Chen YH, Lee AC, Lin HW, Lee EJ (2012)
Nicotinamide inhibits nuclear factor-kappa B translocation after transient focal cerebral ischemia.
Critical care medicine 40, 532-537 [PubMed:21926578]
[show Abstract]
ObjectiveWe explored the putative anti-inflammatory effects of nicotinamide against experimental stroke.DesignProspective laboratory study.SettingResearch laboratory in a university teaching hospital.SubjectsAdult male Sprague-Dawley rats (250-300 g).InterventionsThe antioxidant, radical scavenging, and anti-inflammatory actions of nicotinamide were evaluated using a panel of acellular assays and lipopolysaccharide-stimulated RAW 264.7 and BV2 cells. Animals were subjected to transient middle cerebral artery occlusion for 90 mins. Nicotinamide (500 mg/kg) or vehicle was given intravenously at reperfusion onset.Measurements and main resultsNicotinamide effectively inhibited nuclear factor-κB translocation and binding activity as well as the production of tumor necrosis factor-α, nitrite/nitrate, and interleukin-6 in the lipopolysaccharide-stimulated RAW 264.7 and BV2 cells (p < .05, respectively) but exhibited weak antioxidant and radical-scavenging actions. Relative to controls, nicotinamide-treated animals had significant reductions in neutrophil and macrophage/activated microglial infiltration in the ischemic brain by 53% and 77% (p < .05, respectively). Additionally, nicotinamide significantly attenuated phosphorylation of nuclear factor-κB's inhibitory protein, nuclear factor-κB translocation and binding activity, and the synthesis of inducible nitric oxide in the ischemic brain (p < .05, respectively). Consequently, nicotinamide effectively reduced brain infarction and improved neurobehavioral outcome by 43% and 50% (p < .05, respectively).ConclusionsNicotinamide effectively attenuated postischemic nuclear factor-kappa]B activation and exhibited robust anti-inflammatory actions against ischemic stroke. | Williams AC, Hill LJ, Ramsden DB (2012)
Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra.
Current gerontology and geriatrics research 2012, 302875 [PubMed:22536229]
[show Abstract]
Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson's, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs. | Ferreira RG, Matsui TC, Godin AM, Gomides LF, Pereira-Silva PE, Duarte ID, Menezes GB, Coelho MM, Klein A (2012)
Neutrophil recruitment is inhibited by nicotinamide in experimental pleurisy in mice.
European journal of pharmacology 685, 198-204 [PubMed:22543086]
[show Abstract]
Several emerging lines of evidence support an anti-inflammatory role for nicotinamide and other vitamin B components. However, the mechanisms underlying their activity remain unclear. In the present study, we investigated the ability of nicotinamide to inhibit both neutrophil recruitment in IL-8-, LTB(4)- or carrageenan-induced pleurisy in mice and the rolling and adherence of neutrophils. Nicotinamide inhibited IL-8-, LTB(4)- and carrageenan-induced neutrophil migration, KC production and carrageenan-induced neutrophil rolling and adherence. We propose that the effects of nicotinamide in inhibiting neutrophil recruitment in carrageenan-induced pleurisy may be due to the ability of nicotinamide to inhibit the action of IL-8 and LTB(4), decrease KC production, and inhibit early events that regulate leukocyte migration from blood vessels into tissue. | Dan L, Klimenkova O, Klimiankou M, Klusman JH, van den Heuvel-Eibrink MM, Reinhardt D, Welte K, Skokowa J (2012)
The role of sirtuin 2 activation by nicotinamide phosphoribosyltransferase in the aberrant proliferation and survival of myeloid leukemia cells.
Haematologica 97, 551-559 [PubMed:22207684]
[show Abstract]
BackgroundInhibitors of nicotinamide phosphoribosyltransferase have recently been validated as therapeutic targets in leukemia, but the mechanism of leukemogenic transformation downstream of this enzyme is unclear.Design and methodsHere, we evaluated whether nicotinamide phosphoribosyltransferase's effects on aberrant proliferation and survival of myeloid leukemic cells are dependent on sirtuin and delineated the downstream signaling pathways operating during this process.ResultsWe identified significant upregulation of sirtuin 2 and nicotinamide phosphoribosyltransferase levels in primary acute myeloid leukemia blasts compared to in hematopoietic progenitor cells from healthy individuals. Importantly, specific inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 significantly reduced proliferation and induced apoptosis in human acute myeloid leukemia cell lines and primary blasts. Intriguingly, we found that protein kinase B/AKT could be deacetylated by nicotinamide phosphoribosyltransferase and sirtuin 2. The anti-leukemic effects of the inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 were accompanied by acetylation of protein kinase B/AKT with subsequent inhibition by dephosphorylation. This leads to activation of glycogen synthase kinase-3 β via diminished phosphorylation and, ultimately, inactivation of β-catenin by phosphorylation.ConclusionsOur results provide strong evidence that nicotinamide phosphoribosyltransferase and sirtuin 2 participate in the aberrant proliferation and survival of leukemic cells, and suggest that the protein kinase B/AKT/ glycogen synthase kinase-3 β/β-catenin pathway is a target for inhibition of nicotinamide phosphoribosyltransferase or sirtuin 2 and, thereby, leukemia cell proliferation. | Sun WP, Li D, Lun YZ, Gong XJ, Sun SX, Guo M, Jing LX, Zhang LB, Xiao FC, Zhou SS (2012)
Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives.
Hypertension research : official journal of the Japanese Society of Hypertension 35, 180-185 [PubMed:21918528]
[show Abstract]
Nicotinamide and catecholamines are both degraded by S-adenosylmethionine-dependent methylation. Whether excess nicotinamide affects the degradation of catecholamines is unknown. The aim of this study was to investigate the effect of nicotinamide on the methylation status of the body and methylation-mediated catecholamine degradation in both normotensives and hypertensives. The study was conducted in 19 normotensives and 27 hypertensives, using a nicotinamide-loading test (100 mg orally). Plasma nicotinamide, N(1)-methylnicotinamide, homocysteine (Hcy), betaine, norepinephrine, epinephrine, normetanephrine and metanephrine levels before and 5 h after nicotinamide loading were measured. Compared with normotensives, hypertensives had higher baseline (fasting) levels of plasma nicotinamide, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative. Nicotinamide loading induced a significant increase in the levels of plasma N(1)-methylnicotinamide and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives. Moreover, nicotinamide-loading significantly increased plasma Hcy levels, but decreased plasma normetanephrine levels in normotensives. The baseline levels of plasma epinephrine in hypertensives were similar to those of normotensives, but the post-nicotinamide-loading levels of plasma epinephrine in hypertensives were higher than those of normotensives. This study demonstrated that excess nicotinamide might deplete the labile methyl pool, increase Hcy generation and inhibit catecholamine degradation. It also revealed that hypertensives had an abnormal methylation pattern, characterized by elevated fasting plasma levels of unmethylated substrates, nicotinamide, Hcy and norepinephrine. Therefore, it seems likely that high nicotinamide intake may be involved in the pathogenesis of Hcy-related cardiovascular disease. | Park SY, Lee KB, Lee MJ, Bae SC, Jang JJ (2012)
Nicotinamide inhibits the early stage of carcinogen-induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth.
Journal of cellular physiology 227, 899-908 [PubMed:21503886]
[show Abstract]
Hepatocellular carcinoma (HCC) can cause severe complications, resulting in a high incidence of recurrence after treatment of the primary tumor. Recently, we have shown that nicotinamide effectively inhibits the growth and progression of bladder tumors by up-regulating RUNX3 and p300 expression. Therefore, in this study, the efficacy and inhibitory mechanisms of nicotinamide against HCC were investigated in mice and HCC cell lines, respectively. To evaluate the inhibitory effects of nicotinamide on HCC development, mice were injected with diethylnitrosamine (DEN) and simultaneously treated with 1% nicotinamide. Also, the effect of nicotinamide on human HCC cell lines was assessed by measuring caspase activity, cell proliferation, and DNA content using immunoblot analysis and reverse-transcriptase polymerase chain reaction. It was found that nicotinamide significantly inhibited the development of pre-neoplastic lesions (foci and adenomas) during the early stages of HCC. Furthermore, nicotinamide inhibited cell proliferation and induced mitochondria-mediated apoptosis in HCC cell lines. It also increased the expression of p21, and the expression and acetylation of p53. These results strongly suggest that nicotinamide inhibits the progression of early-stage HCC and may contribute to the induction of apoptosis and the inhibition of proliferation of HCC cells. Taken together, the results of this study indicate that nicotinamide is a potential chemopreventive agent, i.e., it may prevent the progression of early HCC development and/or the recurrence of HCC after primary treatment. | Ullah N, Ullah I, Lee HY, Naseer MI, Seok PM, Ahmed J, Kim MO (2012)
Protective function of nicotinamide against ketamine-induced apoptotic neurodegeneration in the infant rat brain.
Journal of molecular neuroscience : MN 47, 67-75 [PubMed:22160932]
[show Abstract]
During development, anesthetics activate neuroapoptosis and produce damage in the central nervous system that leads to several types of neurological disorders. A single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain activated the apoptotic cascade and caused extensive neuronal cell death in the forebrain. In this study, we investigated the protective effect of nicotinamide against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell death induced by ketamine was associated with the induction of Bax, release of cytochrome c into the cytosol, and activation of caspase-3. One single dose of 1 mg/g nicotinamide was administered to a developing rat and was found to inhibit ketamine-induced neuroapoptosis by downregulating Bax, inhibiting cytochrome c release from mitochondria into cytosol, and inhibiting the expression of activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine-induced cell death occurred through apoptosis and that it was inhibited by nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead cells in the cortex and thalamus after ketamine treatment; treatment with nicotinamide reduced the number of dead cells in these brain regions. Our findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss in the developing rat brain and is a promising therapeutic and neuroprotective agent for the treatment of neurodevelopmental disorders. | Wang H, Cheng H, Wang K, Wen T (2012)
Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells.
Journal of neural transmission (Vienna, Austria : 1996) 119, 1307-1315 [PubMed:22407380]
[show Abstract]
Histone deacetylase inhibitors are involved in proliferation, apoptosis, cell cycle, mRNA transcription, and protein expression in various cells. However, the molecular mechanism underlying such functions is still not fully clear. In this study, we used C17.2 neural stem cell (NSC) line as a model to evaluate the effects of nicotinamide and trichostatin A (TSA) on cell characteristics. Results show that nicotinamide and TSA greatly inhibit cell growth, lead to cell morphology changes, and effectively induce cell apoptosis in a dose-dependent manner. Western blot analyses confirmed that nicotinamide significantly decreases the expression of bcl-2 and p38. Further insight into the molecular mechanisms shows the suppression of phosphorylation in eukaryotic initiation factor 4E-binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of bcl-2 and p38 and phosphorylation of 4EBP1 by TSA. However, both nicotinamide and TSA significantly increase the expression of cytochrome c (cyt c). These results strongly suggest that bcl-2, p38, cyt c, and p-4EBP1 could suppress proliferation and induce apoptosis of C17.2 NSCs mediated by histone deacetylase inhibitors, nicotinamide and TSA, involving different molecular mechanisms. | Peterson TC, Anderson GD, Kantor ED, Hoane MR (2012)
A comparison of the effects of nicotinamide and progesterone on functional recovery of cognitive behavior following cortical contusion injury in the rat.
Journal of neurotrauma 29, 2823-2830 [PubMed:23016598]
[show Abstract]
The primary goal of this study was to compare clinically relevant doses of progesterone and nicotinamide within the same injury model. Progesterone has been shown to reduce edema and inflammation and improve functional outcomes following brain injury. Nicotinamide has also been shown to be an effective neuroprotective agent in a variety of neurological injury models. In the current study, nicotinamide was administered beginning 4 h post-cortical contusion injury (CCI) with a loading dose (75 mg/kg, i.p.) combined with continuous infusion (12 mg/h/kg, s.c.) for 72 h post-injury. Progesterone was administered beginning 4 h post-CCI at a dose of 10 or 20 mg/kg, i.p. every 12 h for 72 h. This resulted in the following groups: Injured-nicotinamide treated, Injured-progesterone-10 treated, Injured-progesterone-20 treated, Injured-vehicle treated, and Sham. Functional recovery was assessed with two spatial memory tasks in the Morris water maze (MWM) the acquisition of a reference memory task and a reversal learning task. Neuropathological assessments were conducted in the cortex and hippocampus. It was found that both progesterone (10 mg/kg) and nicotinamide improved reference memory acquisition and reversal learning in the MWM compared with vehicle treatment. The lower dose of progesterone and nicotinamide also reduced tissue loss in the injured cortex and ipsilateral hippocampus compared with vehicle. The beneficial effects of progesterone appear to be dose dependent with the lower 10 mg/kg dose producing significant effects that were not observed at the higher dose. Direct comparison between nicotinamide and low dose progesterone appears to suggest that both are equally effective. The general findings of this study suggest that both nicotinamide and progesterone produce significant improvements in recovery of function following CCI. | Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A, European Uremic Toxin Work Group (2012)
Normal and pathologic concentrations of uremic toxins.
Journal of the American Society of Nephrology : JASN 23, 1258-1270 [PubMed:22626821]
[show Abstract]
An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD. | In S, Lee DS, Choi B, Kim MJ (2012)
Nicotinamide induces male-specific body weight loss in the postnatal period through molecular regulation of the hypothalamus and liver.
Neuroscience letters 530, 166-171 [PubMed:23043891]
[show Abstract]
Molecular mechanisms of body weight control have been discovered recently and much research focuses on the hypothalamic regulation of food intake and the hepatic regulation of glucose utility. We previously reported that postnatal nicotinamide treatment reduced brain dopamine and body weight. To further investigate the differential effects of nicotinamide-mediated body weight loss, nicotinamide (i.p. 100mg/kg) was injected into postnatal and adult mice twice a week for 4 weeks. Interestingly, following nicotinamide treatment, male postnatal mice displayed reduced body weight and spontaneous motor activity. No significant changes were observed in adult and postnatal female mice or adult male mice following nicotinamide treatment. In male postnatal mice, hypothalamic agouti-related peptide (AGRP) and proopiomelanocortin (POMC) levels were increased in the arcuate nucleus following nicotinamide treatment. Neuropeptide Y (NPY) levels were unchanged in both male and female mice. Additionally, nicotinamide-injected male postnatal mice had increased glucose 6-phosphatase (G6Pase) and decreased phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These results indicate that hypothalamic POMC and hepatic PEPCK are important molecules that mediate nicotinamide-induced weight loss in postnatal male mice. | Chow SF, Chen M, Shi L, Chow AH, Sun CC (2012)
Simultaneously improving the mechanical properties, dissolution performance, and hygroscopicity of ibuprofen and flurbiprofen by cocrystallization with nicotinamide.
Pharmaceutical research 29, 1854-1865 [PubMed:22359146]
[show Abstract]
PurposeTo be fully exploitable in both formulation and manufacturing, a drug cocrystal needs to demonstrate simultaneous improvement of multiple key pharmaceutical properties over the pure drug crystal. The present work was aimed at investigating such feasibility with two model profen-nicotinamide cocrystals.MethodsPhase pure 1:1 ibuprofen-nicotinamide and flurbiprofen-nicotinamide cocrystals were prepared from solutions through rapid solvent removal using rotary evaporation,and characterized by DSC, PXRD, FTIR, phase solubility measurements, equilibrium moisture sorption analysis, dissolution testing and tabletability analysis.ResultsTemperature-composition phase diagrams constructed from DSC data for each profen and nicotinamide crystal revealed the characteristic melting point of the 1:1 cocrystal as well as the eutectic temperatures and compositions. Both cocrystals exhibited higher intrinsic dissolution rates than the corresponding profens. The cocrystals also sorbed less moisture and displayed considerably better tabletability than the individual profens and nicotinamide.ConclusionsPhase behaviors of 1:1 profen-nicotinamide cocrystal systems were delineated by constructing their temperature-composition phase diagrams. Cocrystallization with nicotinamide can simultaneously improve tableting behavior, hygroscopicity, and dissolution performance of ibuprofen and flurbiprofen. This could pave the way for further development of such cocrystal systems into consistent, stable, efficacious and readily manufacturable drug products. | Tong DL, Zhang DX, Xiang F, Teng M, Jiang XP, Hou JM, Zhang Q, Huang YS (2012)
Nicotinamide pretreatment protects cardiomyocytes against hypoxia-induced cell death by improving mitochondrial stress.
Pharmacology 90, 11-18 [PubMed:22699421]
[show Abstract]
Background/aimsNicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes.MethodsCultured rat cardiomyocytes were pretreated with nicotinamide, subjected to hypoxia for 6 h, and then cell necrosis and apoptosis were examined. The effects of nicotinamide pretreatment on hypoxia-induced reactive oxygen species (ROS) formation, antioxidant enzyme expression, nicotinamide adenine dinucleotide (NAD(+)) and nicotinamide adenine dinucleotide phosphate (NADP(+)) levels, adenosine triphosphate (ATP) production and mitochondrial membrane potential were tested to elucidate the underlying mechanisms.ResultsBased on the findings that nicotinamide treatment decreased protein expression of receptor-interacting protein (RIP; a marker for cell necrosis) and cleaved caspase-3 (CC3; a marker for cell apoptosis) in normoxic cardiomyocytes, we found that it dramatically reduced hypoxia-induced necrosis and apoptosis in cardiomyocytes. The underlying mechanisms of these effects are associated with the fact that it increased protein expression of superoxide dismutase and catalase, increased intracellular levels of NAD(+) and ATP concentration, decreased mitochondrial ROS generation and prevented the loss of mitochondrial membrane potential.ConclusionAll of these results indicate that nicotinamide pretreatment protects cardiomyocytes by improving mitochondrial stress. Our study provides a new clue for the utilization of nicotinamide in therapies for ischemic heart disease. | Fischer F, Gertz M, Suenkel B, Lakshminarasimhan M, Schutkowski M, Steegborn C (2012)
Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition.
PloS one 7, e45098 [PubMed:23028781]
[show Abstract]
Sirtuins are protein deacylases regulating metabolism and aging processes, and the seven human isoforms are considered attractive therapeutic targets. Sirtuins transfer acyl groups from lysine sidechains to ADP-ribose, formed from the cosubstrate NAD(+) by release of nicotinamide, which in turn is assumed to be a general Sirtuin inhibitor. Studies on Sirtuin regulation have been hampered, however, by shortcomings of available assays. Here, we describe a mass spectrometry-based, quantitative deacylation assay not requiring any substrate labeling. Using this assay, we show that the deacetylation activity of human Sirt5 features an unusual insensitivity to nicotinamide inhibition. In contrast, we find similar values for Sirt5 and Sirt3 for the intrinsic NAD(+) affinity as well as the apparent NAD(+) affinity in presence of peptide. Structure comparison and mutagenesis identify an Arg neighboring to the Sirt5 nicotinamide binding pocket as a mediator of nicotinamide resistance, and statistical sequence analyses along with testing further Sirtuins reveal a network of coevolved residues likely defining a nicotinamide-insensitive Sirtuin deacetylase family. The same Arg was recently reported to render Sirt5 a preferential desuccinylase, and we find that this Sirt5 activity is highly sensitive to nicotinamide inhibition. Analysis of Sirt5 structures and activity data suggest that an Arg/succinate interaction is the molecular basis of the differential nicotinamide sensitivities of the two Sirt5 activities. Our results thus indicate a Sirtuin subfamily with nicotinamide-insensitive deacetylase activity and suggest that the molecular features determining nicotinamide sensitivity overlap with those dominating deacylation specificity, possibly suggesting that other subfamily members might also prefer other acylations than acetylations. | Thanos SM, Halliday GM, Damian DL (2012)
Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans.
The British journal of dermatology 167, 631-636 [PubMed:22709272]
[show Abstract]
BackgroundThe immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown.ObjectivesTo determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans.MethodsTwenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression.ResultsHigh irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P < 0·0001); topical and oral nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P < 0·0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045).ConclusionsWhile the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates. | Sung JH, Kim MO, Koh PO (2012)
Nicotinamide prevents the down-regulation of MEK/ERK/p90RSK signaling cascade in brain ischemic injury.
The Journal of veterinary medical science 74, 35-41 [PubMed:21891976]
[show Abstract]
Nicotinamide attenuates neuronal cell death related to focal cerebral ischemic injury. This study investigated whether nicotinamide exerts a neuroprotective effect through the activation of Raf- mitogen-activated protein kinase kinase (MEK)-ERK and its downstream targets, including p90 ribosomal S6 kinase (p90RSK) and Bad. Adult male Sprague-Dawley rats were treated with nicotinamide (500 mg/kg) or vehicle 2 hr after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24 hr after MCAO. In the present study, nicotinamide significantly reduces the volume of infarct regions and decreases the number of positive cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in the cerebral cortex. Nicotinamide prevents injury-induced decrease in Raf-1, MEK1/2, and ERK1/2 phosphorylation. As part of the downstream cascade, nicotinamide inhibits the injury-induced decrease in p90RSK and Bad phosphorylation. Moreover, nicotinamide prevents the injury-induced increase in cleaved caspase-3 levels. These findings suggest that nicotinamide protects neuronal cells against cerebral ischemic injury and that MEK-ERK-p90RSK cascade activation by nicotinamide contributes to these neuroprotective effects. | Koh PO (2012)
Nicotinamide attenuates the decrease of astrocytic phosphoprotein PEA-15 in focal cerebral ischemic injury.
The Journal of veterinary medical science 74, 377-380 [PubMed:22067079]
[show Abstract]
Nicotinamide exerts neuroprotective effects against focal cerebral ischemic injury. Phosphoprotein enriched in astrocytes 15 (PEA-15) is prominently expressed in astrocytes that exert broad anti-apoptotic functions. This study investigated whether nicotinamide modulates PEA-15 and levels of two phosphorylated PEA-15 (Serine 104 and 116) in an animal model of middle cerebral artery occlusion (MCAO)-induced injury. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after the onset of MCAO and cerebral cortices were collected at 24 hr after MCAO. In a proteomic approach, MCAO induced decreases of PEA-15 levels, while nicotinamide treatment attenuated the injury-induced decrease in PEA-15. The results of Western blot analysis suggest that nicotinamide prevented injury-induced reduction in phospho-PEA-15 (Serine 104) and phospho-PEA-15 (Serine 116) levels. The phosphorylation of PEA-15 exerts anti-apoptotic functions, and reduction of PEA-15 phosphorylation leads to apoptotic cell death. These results suggest that nicotinamide exerts a neuroprotective effect by attenuating the injury-induced decreases of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) proteins. | Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM (2009)
Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.
Nature 457, 910-914 [PubMed:19212411]
[show Abstract]
Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity. | Lee JY, Ahn K, Jang BG, Park SH, Kang HJ, Heo JI, Ko YJ, Won MH, Tae-Cheon Kang, Jo SA, Kim MJ (2009)
Nicotinamide reduces dopamine in postnatal hypothalamus and causes dopamine-deficient phenotype.
Neuroscience letters 461, 163-166 [PubMed:19539713]
[show Abstract]
Dopamine is an important neurotransmitter in the human central nervous system and also plays a key role in the development of postnatal brains. We previously reported that nicotinamide, a SIRT1 inhibitor, regulates tyrosine hydroxylase (TH) expression in vitro. To investigate the effect of nicotinamide-mediated TH regulation in vivo, nicotinamide was chronically injected into neonatal mice. Interestingly, nicotinamide-treated mice were smaller in size, and their locomotor activity was reduced. L-DOPA treatment caused hypersensitive locomotor activity that indicates a dopamine-depleted state. These changes seemed to be associated with dopamine metabolism in hypothalamus, since dopamine in hypothalamus was reduced but not in striatum. The present study suggests that the regulation of dopamine metabolism during the postnatal development is important and the underlying molecular mechanisms may be associated with SIRT1 signaling. | Cimadamore F, Curchoe CL, Alderson N, Scott F, Salvesen G, Terskikh AV (2009)
Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death.
Stem cells (Dayton, Ohio) 27, 1772-1781 [PubMed:19544437]
[show Abstract]
Abundant cell death is observed when human embryonic stem cells (hESCs) undergo neuralization, a critical first step for future cell-based therapies addressing neurodegeneration. Using hESC neuralization as an in vitro model of human development, we demonstrated that the developing neuroepithelium acquires increased susceptibility to spontaneous cell death. We found that poly(ADP-ribose) polymerase-1 (PARP1)/apoptosis-inducing factor (AIF)-mediated cell death (parthanatos) is a dominant mechanism responsible for cell loss during hESC neuralization. The demise of neural progenitor cells, at least in part, is due to decreased endogenous antioxidant defenses and enhanced reactive oxygen species leakage from mitochondria fuelled by nonphysiological culture conditions. Under such conditions, PARP1 overactivation triggered cell death through the mitochondrial-nuclear translocation of AIF. Blocking PARP1 activity with small hairpin RNA interference or nicotinamide dramatically enhanced hESC neuralization, providing optimal survival of the developing neuroepithelium. Because nicotinamide is a physiological metabolite, our results raise the possibility that neural stem/progenitor cell survival in vivo requires a metabolic niche. We argue that small natural metabolites provide a powerful physiological tool to optimize hESC differentiation compatible with the requirements of regenerative medicine. | Slomka M, Zieminska E, Lazarewicz J (2008)
Nicotinamide and 1-methylnicotinamide reduce homocysteine neurotoxicity in primary cultures of rat cerebellar granule cells.
Acta neurobiologiae experimentalis 68, 1-9 [PubMed:18389009]
[show Abstract]
Nicotinamide is an important cofactor in many metabolic pathways and a known neuroprotective substance, while its methylated product, 1-methylnicotinamide, is a suspected neurotoxin. Homocysteine is a risk factor in Alzheimer's disease and neurodegeneration, causing inhibition of methylation processes and inducing excitotoxicity. In this study, using primary cultures of rat cerebellar granule cells and propidium iodide staining, we investigated the neurotoxicity of nicotinamide and 1-methylnicotinamide, and their neuroprotective potential in acute and sub-acute homocysteine neurotoxicity. Our results demonstrated that nicotinamide and 1-methylnicotinamide applied for 24 h to cultures at concentrations of up to 25 mM had no effect on neuronal viability. Moreover, nicotinamide at concentrations of 5-20 mM and 1-methylnicotinamide at 1-10 mM applied to cells 24 h before, and for 24 h after an acute 30 min application of 25 mM D,L homocysteine, reduced neuronal damage. 1-Methylnicotinamide at concentrations of 250 and 500 muM showed neuroprotective activity during a sub-acute 24-h exposure to 2.5 mM D,L-homocysteine, while 5 and 25 mM nicotinamide also evoked neuroprotection. These findings do not support suggestions that 1-methylnicotinamide may act as an endogenous neurotoxic agent; rather, they indicate the neuroprotective ability of nicotinamide and 1-methylnicotinamide in homocysteine neurotoxicity. The exact mechanisms of this neuroprotection are unclear and require further investigation. | Biedroń R, Ciszek M, Tokarczyk M, Bobek M, Kurnyta M, Słominska EM, Smoleński RT, Marcinkiewicz J (2008)
1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages.
Archivum immunologiae et therapiae experimentalis 56, 127-134 [PubMed:18373238]
[show Abstract]
Introduction1-Methylnicotinamide (MNA), a major metabolite of nicotinamide (NA), is known to exert anti-inflammatory effects in vivo. Treatment of inflammatory skin diseases by topical application of MNA provides certain advantages over the use of NA. However, in contrast to NA, the molecular mechanisms of the anti-inflammatory properties of MNA are not well known. In this study the influence of exogenous MNA and NA in vivo on the generation of inflammatory mediators by macrophages (Mvarphi) was investigated.Materials and methodsPeritoneal Mvarphi of CBA/J mice were activated in vitro with lipopolysaccharide and incubated with MNA or NA. The effect of these compounds on biological functions of Mvarphi was measured by evaluation of the production of reactive oxygen species (ROS) by luminol-dependent chemiluminescence, cytokines and prostaglandin E(2) (PGE(2)) by ELISA, and nitric oxide (NO) by the Griess method. Moreover, the expressions of inducible NO synthase and cyclooxygenase-2 were measured by Western blotting.ResultsIt was shown that at non-cytotoxic concentrations, NA inhibits the production of a variety of pro-inflammatory agents, such as tumor necrosis factor alpha, interleukin 6, NO, PGE(2), and the generation of ROS. In contrast to NA, exogenous MNA inhibited only the generation of ROS, while its effect on the synthesis of other mediators was negligible.ConclusionsThese results indicate that the anti-inflammatory properties of MNA demonstrated previously in vivo do not depend on its capacity to suppress the functions of immune cells, but more likely may be related to its action on vascular endothelium. The authors suggest that the limited permeability for exogenous MNA, in contrast to that for NA, may be responsible for its lack of suppressor activity against Mvarphi. | Vaca P, Berná G, Araujo R, Carneiro EM, Bedoya FJ, Soria B, Martín F (2008)
Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells.
Experimental cell research 314, 969-974 [PubMed:18234191]
[show Abstract]
The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice. Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells. | Slomka M, Zieminska E, Salinska E, Lazarewicz JW (2008)
Neuroprotective effects of nicotinamide and 1-methylnicotinamide in acute excitotoxicity in vitro.
Folia neuropathologica 46, 69-80 [PubMed:18368629]
[show Abstract]
Nicotinamide (NAM), an important cofactor in many metabolic pathways, exhibits at high doses neuroprotective abilities of an unclear mechanism. In the present study we evaluated the unknown protective capability of its immediate metabolite 1-methylnicotinamide (MNA) in comparison to NAM in primary cultures of rat cerebellar granule cells (CGC) submitted to acute excitotoxicity. Neurotoxicity was evaluated with propidium iodide staining 24 h after 30 min exposure to glutamate (GLU) and NMDA. NAM and MNA reduced NMDA toxicity only at 25 mM concentration, while neurotoxicity of 0.5 mM GLU was slightly diminished only by 25 mM NAM. Both compounds at 25 mM reduced GLU-induced 45Ca uptake and dose-dependently inhibited NMDA-induced 45Ca accumulation. Neither NAM nor MNA interfered with GLU-evoked intracellular calcium transients evaluated with calcium orange fluorescent probe or inhibited [3H]MK-801 binding to rat cortical membranes. NAM and MNA failed to change GLU-evoked decrease in mitochondrial membrane potential monitored using the fluorescent dye rhodamine 123. Analysis with a hydroperoxide-sensitive fluorescent probe demonstrated significant reduction by 20 and 25 mM MNA, but not NAM, of oxidative stress in cultures after 1 h treatment with GLU. CGC accumulated radiolabelled NAM and MNA in a time and concentration dependent manner, NAM being transported more rapidly. These findings demonstrate that weak neuroprotective ability of MNA in excitotoxicity, accompanied by incomplete stabilization of calcium imbalance and lessening of oxidative stress, is not connected with direct inhibition of NMDA receptors. The exact mechanisms of these effects require further investigation. | Zhang LH, Kamanna VS, Zhang MC, Kashyap ML (2008)
Niacin inhibits surface expression of ATP synthase beta chain in HepG2 cells: implications for raising HDL.
Journal of lipid research 49, 1195-1201 [PubMed:18316796]
[show Abstract]
Niacin is an effective agent for raising HDL, but its cellular target sites are largely unknown. We examined effects of niacin on the surface expression of ATP synthase beta chain, a newly described HDL/apolipoprotein A-I (apoA-I) receptor for HDL endocytosis, in HepG2 cells. A significant amount of immunodetectable beta chain was observed on the surface of HepG2 cells, which was competitively displaced by apoA-I. Niacin treatment reduced the surface expression of beta chain in HepG2 cells by approximately 27%, and decreased (125)I-labeled HDL uptake up to approximately 35%. However, nicotinamide, a niacin metabolite that does not have clinical lipid effects, exhibited weaker inhibition on the beta chain cell surface expression, and failed to show inhibitory action on (125)I-labeled HDL uptake. Furthermore, anti-beta chain antibody significantly reduced (125)I-labeled HDL uptake and abolished the inhibitory effect of niacin. Niacin did not change beta chain mRNA expression. These data suggest that niacin inhibits cell surface expression of the ATP synthase beta chain, leading to reduced hepatic removal of HDL protein, thus implicating a potential cellular target for niacin action to raise HDL. | Boivin A, Gaumer S, Sainsard-Chanet A (2008)
Life span extension by dietary restriction is reduced but not abolished by loss of both SIR2 and HST2 in Podospora anserina.
Mechanisms of ageing and development 129, 714-721 [PubMed:18930755]
[show Abstract]
Dietary restriction (DR) extends life span of many organisms, from yeast to mammals. The question of whether or not the SIR2 protein functions to mediate life span extension in response to DR remains debated. In this paper, we studied the relationship between SIR2 and DR in the filamentous fungus Podospora anserina. We show that the loss of PaSir2, PaHst2 or PaPnc1 does not alter life span under standard conditions. PaHst2 is the closest paralog of PaSir2 and the ortholog of yeast HST2 and PaPnc1 is the ortholog of the yeast PNC1 which encodes a nicotinamidase that deaminates nicotinamide, a natural inhibitor of SIR2. As observed for other organisms, overexpression of PaSir2 weakly increases life span under standard condition. Under DR conditions, deletion of the PaSir2 or PaHst2 genes induce a significant reduction in life span extension, while the double mutant strongly reduces life span extension. However, a clear response to DR subsists in the double mutant, demonstrating that DR acts through a SIR2/HST2 independent pathway. | Hoane MR, Pierce JL, Holland MA, Anderson GD (2008)
Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat.
Neuroscience 154, 861-868 [PubMed:18514428]
[show Abstract]
Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae-forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae-forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population. | Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM (2008)
Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau.
The Journal of neuroscience : the official journal of the Society for Neuroscience 28, 11500-11510 [PubMed:18987186]
[show Abstract]
Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD(+)-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated alpha-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability. | Stevens MJ, Li F, Drel VR, Abatan OI, Kim H, Burnett D, Larkin D, Obrosova IG (2007)
Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats.
The Journal of pharmacology and experimental therapeutics 320, 458-464 [PubMed:17021258]
[show Abstract]
In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues. We report the dose-dependent effects of nicotinamide in an established model of early DPN. Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve conduction velocities and thermal and mechanical algesia were measured by standard electrophysiological and behavioral tests. Malondialdehyde plus 4-hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)-hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl indole and Western blot analysis, respectively. Nicotinamide corrected increased sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and dose-dependently attenuated nerve conduction slowing, as well as mechanical and thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated proteins in human Schwann cells. In conclusion, nicotinamide deserves consideration as an attractive, nontoxic therapy for the treatment of DPN. | Tsuchiya M, Dang N, Kerr EO, Hu D, Steffen KK, Oakes JA, Kennedy BK, Kaeberlein M (2006)
Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast.
Aging cell 5, 505-514 [PubMed:17129213]
[show Abstract]
Two models have been proposed for how calorie restriction (CR) enhances replicative longevity in yeast: (i) suppression of rDNA recombination through activation of the sirtuin protein deacetylase Sir2 or (ii) decreased activity of the nutrient-responsive kinases Sch9 and TOR. We report here that CR increases lifespan independently of all Sir2-family proteins in yeast. Furthermore, we demonstrate that nicotinamide, an inhibitor of Sir2-mediated deacetylation, interferes with lifespan extension from CR, but does so independent of Sir2, Hst1, Hst2, and Hst4. We also find that 5 mm nicotinamide, a concentration sufficient to inhibit other sirtuins, does not phenocopy deletion of HST3. Thus, we propose that lifespan extension by CR is independent of sirtuins and that nicotinamide has sirtuin-independent effects on lifespan extension by CR. | Klawitter V, Morales P, Bustamante D, Goiny M, Herrera-Marschitz M (2006)
Plasticity of the central nervous system (CNS) following perinatal asphyxia: does nicotinamide provide neuroprotection?
Amino acids 31, 377-384 [PubMed:16871361]
[show Abstract]
We have investigated the idea that nicotinamide, a non-selective inhibitor of the sentinel enzyme Poly(ADP-ribose) polymerase-I (PARP-1), provides neuroprotection against the long-term neurological changes induced by perinatal asphyxia. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. The effect of perinatal asphyxia on neurocircuitry development was studied in vitro with organotypic cultures from substantia nigra, neostriatum and neocortex, platted on a coverslip 3 days after birth. After approximately one month in vitro (DIV 25), the cultures were treated for immunocytochemistry to characterise neuronal phenotype with markers against the N-methyl-D-aspartate receptor subunit 1 (NR1), the dopamine pacemaker enzyme tyrosine hydroxylase (TH), and nitric oxide synthase (NOS), the enzyme regulating the bioavailability of NO. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyctic and caesarean-delivered pups 24, 48 and 72 h after birth. It was found that nicotinamide treatment prevented the effect of perinatal asphyxia on several neuronal parameters, including TH- and NOS-positive neurite atrophy and NOS-positive neuronal loss; supporting the idea that nicotinamide constitutes a therapeutic alternative for the effects produced by sustained energy-failure conditions, as occurring during perinatal asphyxia. | Draelos ZD, Matsubara A, Smiles K (2006)
The effect of 2% niacinamide on facial sebum production.
Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology 8, 96-101 [PubMed:16766489]
[show Abstract]
BackgroundThe presence of sebum on the face is responsible for both facial shine and the formation of comedonal and inflammatory acne lesions. Sebum control is a goal of many OTC skin care products; however, most currently available products function by absorbing sebum from the face rather than modulating its production.ObjectiveTo demonstrate the effect of topical 2% niacinamide on sebum excretion rates and casual sebum production in Oriental and Caucasian populations.MethodsSeparate clinical trials were conducted in both Japan and the USA to evaluate the effect of topical 2% niacinamide in different ethnic groups. A total of 100 Japanese subjects were enrolled in a double-blind, placebo-controlled comparison between two independent balanced groups. Fifty subjects applied the 2% niacinamide moisturizer to the face for 4 weeks and 50 subjects used a placebo moisturizer for 4 weeks, with sebum excretion rate (SER) measurements taken at baseline, week 2, and week 4. In addition, 30 Caucasian subjects were enrolled in a randomized split-face study for 6 weeks with SER and casual sebum levels (CSL) measured at baseline, week 3, and week 6.ResultsThe results of the Japanese study demonstrated that the SER of the two groups was not significantly different at baseline, but the 2% niacinamide treated group demonstrated significantly lowered SER after 2 and 4 weeks of application. The results were somewhat different in the Caucasian study. After 6 weeks of treatment, the CSL was significantly reduced, but the SER was not significantly reduced.ConclusionsTopical 2% niacinamide may be effective in lowering the SER in Japanese individuals and CSL in Caucasian individuals. | Hoskin PJ, Rojas AM, Phillips H, Saunders MI (2005)
Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide.
Cancer 103, 2287-2297 [PubMed:15834926]
[show Abstract]
BackgroundAccelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON.MethodsAcute and late morbidity was assessed in 105 patients with high-grade superficial or muscle-invasive bladder carcinoma who were given accelerated radiotherapy (50-55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease-free survival, and locoregional control.ResultsNearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20-30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies > or = 3 times per day. By 10-12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency < or = 2 times per hour was approximately 75% in both arms. Incidence of severe hematuria (< or = 25%) and urinary urgency (< or = 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone.ConclusionsHistorical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings. | Draelos ZD, Ertel K, Berge C (2005)
Niacinamide-containing facial moisturizer improves skin barrier and benefits subjects with rosacea.
Cutis 76, 135-141 [PubMed:16209160]
[show Abstract]
A growing body of literature suggests that some moisturizers can improve stratum corneum barrier function, as well as ameliorate dry skin. The clinical signs and symptoms of rosacea, which include increased facial skin dryness and sensitivity, suggest a possible role for such moisturizers as an adjuvant in the management of this condition. This randomized, investigator-blind, controlled observational study (N = 50) was designed to assess whether a niacinamide-containing facial moisturizer would improve the stratum corneum barrier and thus provide a clinical benefit to subjects with rosacea. Subjects with rosacea applied the test moisturizer to their face and to one forearm twice daily for 4 weeks. The other forearm remained untreated as a control. Barrier function on the forearms was assessed instrumentally and using a dimethyl sulfoxide (DMSO) chemical probe. Stratum corneum hydration also was measured instrumentally. The dermatologist investigator evaluated each subject's rosacea condition over the course of the study, and subjects self-assessed their facial skin condition at study end. Instruments provided objective measures of stratum corneum barrier function and hydration on the face. | Bissett DL, Oblong JE, Berge CA (2005)
Niacinamide: A B vitamin that improves aging facial skin appearance.
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 31, 860-5; discussion 865 [PubMed:16029679]
[show Abstract]
BackgroundIn multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness).ObjectiveTo clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity).MethodsFemale white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized). Facial images and instrumental measures were obtained at baseline and at 4-week intervals.ResultsAnalyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved. Corresponding mechanistic information is presented.ConclusionIn addition to previously observed benefits for topical niacinamide, additional effects were identified (improved appearance of skin wrinkles and yellowing and improved elasticity). | Soma Y, Kashima M, Imaizumi A, Takahama H, Kawakami T, Mizoguchi M (2005)
Moisturizing effects of topical nicotinamide on atopic dry skin.
International journal of dermatology 44, 197-202 [PubMed:15807725]
[show Abstract]
BackgroundCertain moisturizers can improve skin barrier function in atopic dermatitis. The effect of topical nicotinamide on atopic dry skin is unknown. We examined the effect of topical nicotinamide on atopic dry skin and compared the results with the effect of white petrolatum in a left-right comparison study.MethodsTwenty-eight patients with atopic dermatitis, with symmetrical lesions of dry skin on both forearms, were enrolled, and were instructed to apply nicotinamide cream containing 2% nicotinamide on the left forearm and white petrolatum on the right forearm, twice daily over a 4- or 8-week treatment period. Transepidermal water loss and stratum corneum hydration were measured by instrumental devices. The amount of the stratum corneum exfoliated by tape stripping (desquamation index) was determined by an image analyzer.ResultsNicotinamide significantly decreased transepidermal water loss, but white petrolatum did not show any significant effect. Both nicotinamide and white petrolatum increased stratum corneum hydration, but nicotinamide was significantly more effective than white petrolatum. The desquamation index was positively correlated with stratum corneum hydration at baseline and gradually increased in the nicotinamide group, but not in the white petrolatum group.ConclusionsNicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis. | Cosmetic Ingredient Review Expert Panel (2005)
Final report of the safety assessment of niacinamide and niacin.
International journal of toxicology 24 Suppl 5, 1-31 [PubMed:16596767]
[show Abstract]
Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic aromatic compounds which function in cosmetics primarily as hair and skin conditioning agents. Niacinamide is used in around 30 cosmetic formulations including shampoos, hair tonics, skin moisturizers, and cleansing formulations. Niacin is used in a few similar product types. The concentration of use of Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders and sprays. Niacin concentrations of use range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in paste masks (mud packs). Both ingredients are accepted for use in cosmetics in Japan and the European Union. Both are GRAS direct food additives and nutrient and/or dietary supplements. Niacinamide may be used in clinical treatment of hypercholesteremia and Niacin in prevention of pellegra and treatment of certain psychological disorders. Both ingredients are readily absorbed from skin, blood, and the intestines and widely distribute throughout the body. Metabolites include N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is primarily through the urinary tract. While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic. Short-term oral, parenteral, or dermal toxicity studies did not identify significant irreversible effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation, was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in actual formulations produced mostly non-irritant reactions, with only some marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide in rabbits produced only marginal irritation. Skin sensitization tests of Niacinamide at 5% during induction and 20% during challenge were negative in guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or without metabolic activation. Niacinamide and Niacin at 2 mg/ml were negative in a chromosome aberration test in Chinese hamster ovary cells, but did produce large structural chromosome aberrations at 3 mg/ml. Niacinamide induced sister chromatid exchanges in Chinese hamster ovary cells, but Niacin did not. Under certain circumstances, Niacinamide can cause an increase in unscheduled DNA synthesis in human lymphocytes treated with UV or a nitrosoguanidine compound. Niacinamide itself was not carcinogenic when administered (1%) in the drinking water of mice. No data on the carcinogenic effect of Niacin were available. Niacinamide can moderate the induction of tumors by established carcinogens. Niacinamide in combination with streptozotocin (a nitrosourea compound) or with heliotrine (a pyrrolizidine alkaloid), produced pancreatic islet tumors. On the other hand, Niacinamide reduced the renal adenomas produced by streptozotocin; and intestinal and bladder tumors induced by a preparation of bracken fern. Niacinamide evaluated in in vitro test systems did affect development, but Niacinamide reduced the reproductive/developmental toxicity of 2-aminonicotinamide-amino-1,3,4-thiadiazole hydrochloride and urethane. Clinical testing of Niacinamide produced no stinging sensation at concentrations up to 10%, use tests produced no irritation at concentrations up to 5%, and a 21-day cumulative irritation test at concentrations up to 5% resulted in no irritancy. Niacinamide was not a sensitizer, nor was it a photosensitizer. The CIR Expert Panel considered that Niacinamide and Niacin are sufficiently similar from a toxicologic standpoint to combine the available data and reach a conclusion on the safety of both as cosmetic ingredients. Overall, these ingredients are non-toxic at levels considerably higher than would be experienced in cosmetic products. Clinical testing confirms that these ingredients are not significant skin irritants, sensitizers or photosensitizers. While certain formulations were marginal to slight ocular irritants, other formulations were not. Niacinamide, while not carcinogenic alone, can modulate the induction of tumors by certain established carcinogens. The Panel noted that the doses in these studies are high relative to the low concentrations at which Niacinamide is used in cosmetic formulations. In neither case (tumor protection or tumor promotion) are these findings considered relevant to the use of Niacinamide at its current low concentrations of use in cosmetics. Both ingredients were considered safe as used in cosmetics. | Avalos JL, Bever KM, Wolberger C (2005)
Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme.
Molecular cell 17, 855-868 [PubMed:15780941]
[show Abstract]
Sir2 enzymes form a unique class of NAD(+)-dependent deacetylases required for diverse biological processes, including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a noncompetitive inhibitor that promotes a base-exchange reaction at the expense of deacetylation. To elucidate the mechanism of nicotinamide inhibition, we determined ternary complex structures of Sir2 enzymes containing nicotinamide. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD(+) binding and catalysis. Based on our structures, we engineered a mutant that deacetylates peptides by using nicotinic acid adenine dinucleotide (NAAD) as a cosubstrate and is inhibited by nicotinic acid. The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism. | Kawasaki E, Abiru N, Eguchi K (2004)
Prevention of type 1 diabetes: from the view point of beta cell damage.
Diabetes research and clinical practice 66 Suppl 1, S27-32 [PubMed:15563975]
[show Abstract]
The hallmark of immune-mediated type 1 diabetes is T cell-mediated destruction of the insulin-producing beta cells in the islets, which results from an imbalance between disease promoting factors and protective elements. The precise mechanisms of beta cell destruction leading to diabetes remain unclear. There are many molecules, including Fas ligand (FasL) and cytokines, such as IL-1, TNF-alpha and IFN-gamma that cause release of other cytokine-mediators that have potential to damage the beta cells. The beta cell-death appears to ultimately be caused by receptor (Fas/FasL)-mediated mechanisms and/or by secretion of cytotoxic molecules (e.g., granzymes, perforin). FasL-mediated beta cell damage might play a role in promoting insulitis and beta cell destruction in autoimmune diabetes in addition to toxic molecules, such as reactive oxygen species (superoxide, hydroxy radical, nitric oxide) or perforin. Furthermore, DNA damage in beta cells leads to poly (ADP-ribose) polymerase-activation which will increase NAD consumption and rapid depletion of NAD compromise ATP production in the cells. Nicotinamide inhibits poly (ADP-ribose) polymerase and reduces nitric oxide accumulation in the NOD pancreas and protect beta cells against radical-induced necrosis. Transgenic mice with beta cell specific overexpression of copper, zinc superoxide dismutase, or thioredoxin are resistant to autoimmune and STZ-induced diabetes. It is apparent that a number of different mechanisms of beta cell destruction are operative in type 1 diabetes. Blockage of multiple pathways, rather than a single pathway, of beta cell-death may, therefore be necessary to fully protect beta cells from destruction and thereby prevent type 1 diabetes. | Takahashi Y, Tanaka A, Nakamura T, Fukuwatari T, Shibata K, Shimada N, Ebihara I, Koide H (2004)
Nicotinamide suppresses hyperphosphatemia in hemodialysis patients.
Kidney international 65, 1099-1104 [PubMed:14871431]
[show Abstract]
BackgroundThe use of calcium- or aluminum-based phosphate binders against hyperphosphatemia is limited by the adverse effects of hypercalcemia or aluminum toxicity in long-term hemodialysis. Because nicotinamide is an inhibitor of sodium-dependent phosphate cotransport in rat renal tubule and small intestine, we examined whether nicotinamide reduces serum levels of phosphorus and intact parathyroid hormone (iPTH) in patients undergoing hemodialysis.MethodsSixty-five hemodialysis patients with a serum phosphorus level of more than 6.0 mg/dL after a 2-week washout of calcium carbonate were enrolled in this study. Nicotinamide was administered for 12 weeks. The starting dose was 500 mg/day, and the dose was increased by 250 mg/day every 2 weeks until serum phosphorus levels were well controlled at less than 6.0 mg/dL. A 2-week posttreatment washout period followed the cessation of nicotinamide. Blood samples were collected every week for measurement of serum calcium, phosphorus, lipids, iPTH, and blood nicotinamide adenine dinucleotide (NAD).ResultsThe mean dose of nicotinamide was 1080 mg/day. The mean blood NAD concentration increased from 9.3 +/- 1.9 nmol/105 erythrocytes before treatment to 13.2 +/- 5.3 nmol/105 erythrocytes after treatment (P < 0.01). The serum phosphorus concentration increased from 5.4 +/- 1.5 mg/dL to 6.9 +/- 1.5 mg/dL with the pretreatment washout, then decreased to 5.4 +/- 1.3 mg/dL after the 12-week nicotinamide treatment (P < 0.0001), and rose again to 6.7 +/- 1.6 mg/dL after the posttreatment washout. Serum calcium levels decreased during the pretreatment washout from 9.1 +/- 0.8 mg/dL to 8.7 +/- 0.7 mg/dL with the cessation of calcium carbonate. No significant changes in serum calcium levels were observed during nicotinamide treatment. Median serum iPTH levels increased with pretreatment washout from 130.0 (32.8 to 394.0) pg/mL to 200.0 (92.5 to 535.0) pg/mL and then decreased from the maximum 230.0 (90.8 to 582.0) pg/mL to 150.0 (57.6 to 518.0) pg/mL after the 12-week nicotinamide treatment (P < 0.05). With nicotinamide, serum high-density lipoprotein (HDL) cholesterol concentrations increased from 47.4 +/- 14.9 mg/dL to 67.2 +/- 22.3 mg/dL (P < 0.0001) and serum low-density lipoprotein (LDL) cholesterol concentrations decreased from 78.9 +/- 18.8 mg/dL to 70.1 +/- 25.3 mg/dL (P < 0.01); serum triglyceride levels did not change significantly.ConclusionNicotinamide may provide an alternative for controlling hyperphosphatemia and hyperparathyroidism without inducing hypercalcemia in hemodialysis patients. | Gallo CM, Smith DL, Smith JS (2004)
Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.
Molecular and cellular biology 24, 1301-1312 [PubMed:14729974]
[show Abstract]
The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase (HDAC) that functions in transcriptional silencing and longevity. The NAD(+) salvage pathway protein, Npt1, regulates Sir2-mediated processes by maintaining a sufficiently high intracellular NAD(+) concentration. However, another NAD(+) salvage pathway component, Pnc1, modulates silencing independently of the NAD(+) concentration. Nicotinamide (NAM) is a by-product of the Sir2 deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase that converts NAM to nicotinic acid. Here we show that recombinant Pnc1 stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, life span, and Hst1-mediated transcriptional repression. Finally, we show that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression. Pnc1, therefore, positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress. | Hyppönen E (2004)
Micronutrients and the risk of type 1 diabetes: vitamin D, vitamin E, and nicotinamide.
Nutrition reviews 62, 340-347 [PubMed:15497767]
[show Abstract]
Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect. | Bartalena L, Tanda ML, Piantanida E, Lai A (2003)
Oxidative stress and Graves' ophthalmopathy: in vitro studies and therapeutic implications.
BioFactors (Oxford, England) 19, 155-163 [PubMed:14757966]
[show Abstract]
Graves' ophthalmopathy (GO) is a disorder of autoimmune origin caused by a complex interplay of endogenous and environmental factors. After recognition of one or more antigens shared by thyroid and orbit, activated T lymphocytes infiltrating the orbit trigger a cascade of events leading to production of cytokines, growth factors and oxygen reactive species. Proliferation of adipocytes and fibroblasts then follows, with an increased synthesis of glycosaminoglycans (GAG), which attract water and cause edema of orbital structures and venous congestion. Proliferation of orbital fibroblasts and adipocytes, both in the retroocular tissue and in the perimysium of extraocular muscles, are among the most important events leading to the increased volume of orbital structures (fibroadipose tissue and extraocular muscles). The contribution of oxygen reactive species to the changes occurring in the orbit is underscored by in vitro studies. Superoxide radical stimulates orbital fibroblasts to proliferate and to produce GAG. Furthermore, hydrogen peroxide induces expression of HLA-DR and heat shock protein-72, involved in antigen recognition and T-lymphocyte recruitment. Cigarette smoking, which is probably the most important environmental factor associated with GO occurrence and maintenance, might also act, among other mechanisms, by enhancing generation of oxygen reactive species and reducing antioxidant production. Substances such as nicotinamide, allopurinol and pentoxifylline reduce superoxide- or hydrogen peroxide-induced proliferation of fibroblasts, GAG production and HLA-DR or HSP-72 expression by GO orbital fibroblasts, possibly through scavenging oxygen free radicals. Two small, non-randomized and/or uncontrolled studies investigated the effects of nicotinamide, allopurinol or pentoxifylline on GO. Favorable results were reported, but data are not fully convincing and the true effectiveness of these agents needs to be verified in randomized, controlled trials enrolling a larger number of patients. It currently seems unlikely that they may find a relevant place in the limited armamentarium available for the management of severe GO. | Ungerstedt JS, Blömback M, Söderström T (2003)
Nicotinamide is a potent inhibitor of proinflammatory cytokines.
Clinical and experimental immunology 131, 48-52 [PubMed:12519385]
[show Abstract]
The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease. | Namazi MR (2003)
Nicotinamide: a potential addition to the anti-psoriatic weaponry.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17, 1377-1379 [PubMed:12890690]
[show Abstract]
Psoriasis is an inflammatory disorder characterized by a T helper type 1 cell cytokine pattern. Increased expression of adhesion molecules, prominent neutrophil accumulation, and increased production of nitric oxide are characteristics of this disorder. Moreover, histamine and proteases are supposed to participate in the pathogenesis of psoriasis. Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-alpha production, nicotinamide produces a mild TH2 bias. Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis and mast cell histamine release. It inhibits nitric oxide synthase mRNA induction and suppresses antigen-induced lymphocyte transformation. Nicotinamide increases the biosynthesis of ceramides, which upon degradation produce sphingosine. Sphingosine inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC. Taken together, it can be reasoned that nicotinamide could be a useful addition to anti-psoriatic armamentarium. The combination of nicotinamide and thalidomide or methotrexate provided a powerful synergistic inhibition of murine collagen-induced arthritis. Nicotinamide decreased the methotrexate-induced hepatotoxicity. The above combinations may prove to have a powerful anti-psoriatic effect as well. As PARP inhibitors could exert anti-retroviral effect, nicotinamide could also be of special value in the treatment of HIV-infected psoriatics. | Sonee M, Martens JR, Evers MR, Mukherjee SK (2003)
The effect of tertiary butylhydroperoxide and nicotinamide on human cortical neurons.
Neurotoxicology 24, 443-448 [PubMed:12782109]
[show Abstract]
It is well known that the generation of oxygen radicals can cause neuronal death by both apoptosis and necrosis, which may lead to the onset of neurodegenerative diseases. In previous in vivo studies, nicotinamide was found to prevent both DNA fragmentation and apoptosis that were induced by free radical generating toxins like tertiary butylhydroperoxide (t-BuOOH). Nicotinamide is a precursor for NAD and is an inhibitor of the enzyme poly(ADP-ribose) polymerase (PARP). However, the effect of nicotinamide on the regulation of pro- and anti-apoptotic proteins in neurons is not clear. In our study, the human cortical neuronal cell line HCN1-A has been used to determine the mechanism of action of nicotinamide at the cellular level. Cell viability studies showed that t-BuOOH treatment (both 100 microM and 1mM) caused significant cell death at 24 and 48h compared to control cells. Pretreatment with 1mM nicotinamide before t-BuOOH administration caused significant reduction in cell death. Moreover, the morphology of HCN1-A cells that were treated with both nicotinamide and t-BuOOH appeared to be closer to control cells when compared to HCN1-A cells treated with only t-BuOOH. Also, t-BuOOH treatment caused an elevation in the levels of the pro-apoptotic proteins p53 and p21/WAF-1 and a reduction in the levels of the anti-apoptotic protein bcl-2 compared to their levels in control HCN1-A cells, while pretreatment with nicotinamide reduced p53 and p21/WAF-1 levels even in the presence of t-BuOOH. However nicotinamide did not seem to alter bcl-2 levels. These results indicate that nicotinamide treatment can protect human neuronal cells from the toxic effects of t-BuOOH. | Kiuchi K, Yoshizawa K, Shikata N, Matsumura M, Tsubura A (2002)
Nicotinamide prevents N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats and C57BL mice.
Experimental eye research 74, 383-392 [PubMed:12014919]
[show Abstract]
In previous studies, it was found that a single systemic administration of N-methyl-N-nitrosourea (MNU) to rats and mice resulted in the retinal degeneration in all treated animals over a 7 day period. Retinal degeneration was due to photoreceptor cell apoptosis that was identical to the apoptosis seen in human retinitis pigmentosa (RP). In the present study, nicotinamide (NAM), a water-soluble B-group vitamin (vitamin B(3)), suppressed photoreceptor cell loss in a dose-dependent manner when administered immediately after MNU treatment. In rats, a dose of NAM >or=25 mg kg(-1) completely suppressed photoreceptor cell loss, and 10 mg kg(-1) partially suppressed photoreceptor cell loss. In mice, doses of 1000 and >or=100 mg kg(-1) were needed for complete and partial suppression, respectively. Thus, rats were more responsive to NAM than mice. The retinoprotective effect of 1000 mg kg(-1) NAM lasted throughout the long-term (35 days) observation period, with no apparent toxicity. Also, in rats, 1000 mg kg(-1) NAM completely suppressed photoreceptor cell loss when administered up to 4 hr after MNU treatment, and partially suppressed photoreceptor cell loss when administered 6 hr after MNU treatment. In mice, administration of NAM 2-6 hr after MNU resulted in partial suppression. NAM did not reduce levels of 7-methyldeoxyguanosine DNA adduct, but did reduce photoreceptor cell apoptosis. Although the mechanism of action underlying this retinoprotection remains to be clarified, NAM may be a potential therapeutic agent for the treatment of retinal degeneration. | Sonee M, Martens JR, Mukherjee SK (2002)
Nicotinamide protects HCN2 cells from the free radical generating toxin, tertiary butylhydroperoxide (t-BuOOH).
Neurotoxicity research 4, 595-599 [PubMed:12709297]
[show Abstract]
In previous studies with mice the oxygen radical generating neurotoxin tertiary butylhydroperoxide (t-BuOOH) was used to mimic the oxidative injury that has been implicated in neurodegenerative diseases. In addition, previous studies have shown that the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide is able to prevent DNA fragmentation and apoptosis that is induced by t-BuOOH in mouse brain. However, the molecular mechanism(s) by which nicotinamide is able to protect human brain cells at the cellular level is not clear. Therefore in this study a cell culture model system with human cortical neuronal cells (HCN2 cells) has been employed where the molecular mechanism(s) of nicotinamide action, both in the presence and absence of t-BuOOH has been studied. Human cortical neurons (HCN2 cells) have been shown to differentiate to a neuron-like morphology. In this study, exposure of HCN2 cells to t-BuOOH resulted in altered morphology and disruption of neuronal differentiation leading to cell death. However, in neurons, which were treated with nicotinamide before being exposed to t-BuOOH, neuronal differentiation was preserved; morphological disruption was prevented and cell death was reduced significantly. Moreover, our studies indicate that nicotinamide is able to prevent the up-regulation of the pro-apoptotic proteins p53 and p21/WAF-1, and the down-regulation of the anti-apoptotic protein bcl-2 that is induced by t-BuOOH in HCN2 cells. Thus this study indicates that nicotinamide protects human brain cells from the toxic effects of free radical generating toxins by regulating the levels of various pro- and anti-apoptotic proteins. | Yang L, Yao Y, Shi Y, Wang X, Shi J (2002)
[Expression of nicotinamide edenine dinucleotide dehydrogenase gene in placenta of patients with pregnancy induced hypertension].
Zhonghua fu chan ke za zhi 37, 660-662 [PubMed:12487919]
[show Abstract]
ObjectiveTo investigate the expression of nicotinamide edenine dinucleotide (NADH) dehydrogenase gene in the placenta of patients with pregnancy induced hypertension (PIH) and the role of NADH dehydrogenase in PIH pathogenesis.MethodsUsing (32)P dATP labeled human NADH dehydrogenase cDNA probe, the expression of NADH dehydrogenase gene in placental tissues of 10 normal late pregnant (NLP) women and 10 PIH patients was detected by dot blot. Mean A of each hybridization dot was measured by image analysis system to compare NADH dehydrogenase mRNA level in PIH placentae with that in NLP placenta.ResultsThe NADH dehydrogenase gene values in patients with PIH and NLP were 21 +/- 6 and 56 +/- 16. The level of NADH dehydrogenase mRNA in PIH placenta was significantly higher than that in normal placenta (P < 0.05).ConclusionElevated expression of NADH dehydrogenase gene may play a role in PIH pathogenesis. | Matuoka K, Chen KY, Takenawa T (2001)
Rapid reversion of aging phenotypes by nicotinamide through possible modulation of histone acetylation.
Cellular and molecular life sciences : CMLS 58, 2108-2116 [PubMed:11814060]
[show Abstract]
Aging appears to be an irreversible process. Here we report that nicotinamide (NAA) can induce rapid and reversible reversion of aging phenotypes in human diploid fibroblasts in terms of cell morphology and senescence-associated beta-galactosidase activity. Although NAA seems to enhance the replicative potential of the cells, it has little effect on their growth rate and life span, suggesting that NAA action is rather separated from the cellular replicative system. The effects are unique to NAA: none ofthe NAA-related compounds examined (an NAD precursor/niacin, NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted similar effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely related to the NAA action. On the other hand, histone acetyltransferase (HAT) activity was elevated in NAA-exposed cells, while in aged cells, HAT activity and histone H4 acetylation were lowered. Taken together, the results suggest that NAA may cause rejuvenation by restoring, at least in part, altered gene expression in aged cells through its activation of HAT. | Li JH, Zhang J (2001)
PARP inhibitors.
IDrugs : the investigational drugs journal 4, 804-812 [PubMed:15995937]
[show Abstract]
Poly(ADP-ribose) polymerase (PARP) catalyzes the biochemical conversion of nicotinamide adenine dinucleotide (NAD+) to poly(ADP-ribose) and nicotinamide, which is a weak feedback inhibitor of the enzyme. Early designs of PARP inhibitors were primarily based on mimicking the structure of nicotinamide and resulted in the identification and widespread use of benzamide analogs as PARP inhibitors. Recent searches for more potent and specific PARP inhibitors, facilitated by the crystal structure of the catalytic domain of PARP, led to several families of amide and lactam derivatives with multiple ring systems. New PARP inhibitors have shown efficacies in several animal disease models of cancer, ischemia and inflammation. | Theisen M, Träger K, Tugtekin I, Stehr A, Ploner F, Georgieff M, Radermacher P, Matĕjovic M (2001)
Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia.
Intensive care medicine 27, 586-592 [PubMed:11355130]
[show Abstract]
ObjectiveTo investigate the effects of nicotinamide (NIC), an inhibitor of poly(ADP-ribose) synthetase (PARS), on intestinal and liver perfusion, O2 kinetics, and energy metabolism over 24 h of hyperdynamic porcine endotoxemia.DesignProspective, randomized, controlled experimental study with repeated measures.SettingAnimal laboratory in a university hospital.SubjectsSixteen pigs, divided into two groups: nine endotoxemic animals without therapy (CON); seven animals treated with NIC.InterventionsPigs were anesthetized, mechanically ventilated, and instrumented. Intravenous E. Coli LPS was continuously infused over 24 h concomitant with fluid resuscitation. After 12 h of endotoxemia continuous i.v. infusion of NIC (10 mg/kg per hour) was administered until the end of the experiment.Measurements and resultsAll animals developed hyperdynamic circulation with sustained increase in cardiac output and progressive fall in mean arterial pressure. NIC maintained blood pressure without affecting CO. Hepato-splanchnic macrocirculation was not modified by the treatment. Nevertheless, although NIC attenuated the progressive rise of ileal mucosal-arterial PCO2 gap, it failed to improve portal venous L/P ratio, a marker of the overall energy state of the portal venous drained viscera. Similarly, neither the increased hepatic venous L/P ratio nor the simultaneous drop in hepatic lactate uptake were influenced by NIC.ConclusionsAlthough NIC maintained hemodynamic stabilization during long-term endotoxemia, it was unable to improve LPS-induced deterioration of the hepato-splanchnic energy metabolism. More potent and selective PARS inhibitors are needed to elucidate the role of a PARS-dependent pathway in a clinically relevant models of sepsis. | Mokudai T, Ayoub IA, Sakakibara Y, Lee EJ, Ogilvy CS, Maynard KI (2000)
Delayed treatment with nicotinamide (Vitamin B(3)) improves neurological outcome and reduces infarct volume after transient focal cerebral ischemia in Wistar rats.
Stroke 31, 1679-1685 [PubMed:10884473]
[show Abstract]
Background and purposeWe have previously shown that nicotinamide (NAm) acutely reduces brain infarction induced by permanent middle cerebral artery occlusion (MCAo) in rats. In this study, we investigate whether NAm may protect against ischemia/reperfusion injury by improving sensory and motor behavior as well as brain infarction volumes in a model of transient focal cerebral ischemia.MethodsForty-eight male Wistar rats were used, and transient focal cerebral ischemia was induced by MCAo for 2 hours, followed by reperfusion for either 3 or 7 days. Animals were treated with either intraperitoneal saline or NAm (500 mg/kg) 2 hours after the onset of MCAo (ie, on reperfusion). Sensory and motor behavior scores and body weight were obtained daily, and brain infarction volumes were measured on euthanasia.ResultsRelative to treatment with saline, treatment with NAm (500 mg/kg IP) 2 hours after the onset of transient focal cerebral ischemia in Wistar rats significantly improved sensory (38%, P<0.005) and motor (42%, P<0.05) neurological behavior and weight gain (7%, P<0.05) up to 7 days after MCAo. The cerebral infarct volumes were also reduced 46% (P<0.05) at 3 days and 35% (P=0.09) at 7 days after MCAo.ConclusionsNAm is a robust neuroprotective agent against ischemia/reperfusion-induced brain injury in rats, even when administered up to 2 hours after the onset of stroke. Delayed NAm treatment improved both anatomic and functional indices of brain damage. Further studies are needed to clarify whether multiple doses of NAm will improve the extent and duration of this neuroprotective effect and to determine the mechanism(s) of action underlying the neuroprotection observed. Because NAm is already used clinically in large doses and has few side effects, these results are encouraging for the further examination of the possible use of NAm as a therapeutic neuroprotective agent in the clinical treatment of acute ischemic stroke. | Anisimov AG, Bolotnikov IA (1997)
[Nicotinamide decreases DNA destabilization in K562 cells treated with AlF(-4)].
Tsitologiia 39, 822-828 [PubMed:9518388]
[show Abstract]
Using trypan blue exclusion test it has been shown that a 18 hour incubation of human erythromyeloleukosis cell line K562 together with AlF(-4) (10 mM NaF + 20 mkM AlCl3) reduced cell proliferation and survival. However, the latter parameter did not change during 4 hours of incubation. Nevertheless, AlF(-4) increased fragmentation of 3H-thymidine-labelled DNA by 2-4 times. This effect may be suppressed by cultivation of cells with 20 mkM nicotinamide (inhibitor of poly(ADP-ribose)polymerase enzyme). We found that incubation of K562 and YAC-1 cells with 10 mM nicotinamide for 24 hours much reduced their susceptibility to non-MHC-restricted lysis by rat spleen cells. This effect may be induced by a share of intracellular NAD+ and NADH from destroyed K562 cells; their concentration in cells increased under the influence of nicotinamide by 3 times, but this effect should be the least because in these conditions nicotinamide does not influence the survival of K562 cells. The effect of nicotinamide in both cases may be explained by suppression of poly(ADP-ribose)polymerase activity and, thus, the rate of DNA reparation. Analysis of AlF(-4) and nicotinamide effects on the K562 cells enables us to suppose that suppression of the K562 proliferation by tetrafluoroaluminate results in accumulation of reversed damages of DNA. | Kamat JP, Devasagayam TP (1996)
Methylene blue plus light-induced lipid peroxidation in rat liver microsomes: inhibition by nicotinamide (vitamin B3) and other antioxidants.
Chemico-biological interactions 99, 1-16 [PubMed:8620561]
[show Abstract]
Methylene blue plus visible light, in the presence of oxygen, induced lipid peroxidation in rat liver microsomes, as assessed by the formation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides and the loss of membrane-bound enzymes. Peroxidation was enhanced by deuteration of the buffer and inhibited by scavengers of singlet oxygen (1O2) and superoxide (O2.-). The damage induced seemed to be mainly due to Type II involving 1O2 and to a lesser extent Type I reactions with O2.- and hydroxyl radical (.OH) as intermediates. Nicotinamide or vitamin B3, an endogenous metabolite occurring at high concentrations in tissues, had a relatively high rate constant of 1.8 x 108 M-1 s-1 with 102 and had a significant inhibitory effect on lipid peroxidation induced by photosensitization. This effect was both time- and concentration-dependent, high inhibition being associated with millimolar concentrations. Chemically related endogenous compounds like tryptophan and isonicotinic acid also had significant inhibitory properties. Similar protective effects were observed with natural antioxidants such as beta-carotene, canthaxanthin, lipoic acid, glutathione, alpha-tocopherol and to a lesser extent ascorbic acid. Nicotinamide was a more effective antioxidant than ascorbic acid. It also showed a similar inhibitory effect against NADPH-ADP-FE3(+)-induced lipid peroxidation. Our results suggest that nicotinamide had significant ability to protect against photosensitization-induced cytotoxicity and cell damage and that it may do so by its ability to react with 102 and other reactive oxygen species. | Baeza N, Moriscot C, Figarella C, Guy-Crotte O, Vialettes B (1996)
Reg protein: a potential beta-cell-specific growth factor?
Diabetes & metabolism 22, 229-234 [PubMed:8767167]
[show Abstract]
Beta-cell regeneration in adult pancreas is usually considered to be limited. However, various animal models suggest that this tissue is still capable of regeneration under certain conditions. Reg protein could be responsible for this replicative process. The reg gene codes for a 166 amino-acid protein usually synthesized and secreted by pancreatic acinar cells but expressed in islet beta cells during experimental regenerative processes in animals (90% pancreatectomy + nicotinamide, or insulinoma tumor removal in rats, or the "wrapping pancreas model" in the hamster). In addition, recombinant rat reg protein can stimulate beta-cell replication in vivo and in vitro. In animal models of Type 1 diabetes mellitus, reg gene overexpression occurs during active phases of diabetogenesis and could be a defence mechanism. During human pancreatic development, reg gene is expressed at an early stage but is not associated with the expression of other pancreatic genes. Conversely, gene expression for reg and insulin are correlated in adult pancreas. Accordingly, reg protein could be a beta-cell-specific growth factor implicated in the maintenance of beta-cell mass, especially in adult pancreas. | Shoemaker JD, Elliott WH (1991)
Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease.
Journal of chromatography 562, 125-138 [PubMed:2026685]
[show Abstract]
Eighty-five clinical urine samples and nineteen urine samples previously found by other laboratories to suggest genetic metabolic defects were prepared for trimethylsilylation by treatment with urease, followed by azeotropic dehydration. The "Target Analyte Search" program provided with the VG Trio 2 gas chromatograph-mass spectrometer required 6 min to quantify 103 compounds relative to endogenous urinary creatinine. This technique has been used to confirm diagnoses including cystinuria, lysinuria, medium-chain acyldehydrogenase deficiency, ornithine transcarbamylase deficiency, aspartylglucosaminuria, methylmalonic, propionic and glutaric acidurias. |
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