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| Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula (CH3)2SO. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water. It has a relatively high boiling point. DMSO is metabolised to compounds that leave a garlic-like taste in the mouth after DMSO is absorbed by skin.
In terms of chemical structure, the molecule has idealized Cs symmetry. It has a trigonal pyramidal molecular geometry consistent with other three-coordinate S(IV) compounds, with a nonbonded electron pair on the approximately tetrahedral sulfur atom.
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Read full article at Wikipedia
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| InChI=1S/C2H6OS/c1-4(2)3/h1-2H3 |
| IAZDPXIOMUYVGZ-UHFFFAOYSA-N |
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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polar aprotic solvent
A solvent with a comparatively high relative permittivity (or dielectric constant), greater than ca. 15, and a sizable permanent dipole moment, that cannot donate suitably labile hydrogen atoms to form strong hydrogen bonds.
radical scavenger
A role played by a substance that can react readily with, and thereby eliminate, radicals.
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
non-narcotic analgesic
A drug that has principally analgesic, antipyretic and anti-inflammatory actions. Non-narcotic analgesics do not bind to opioid receptors.
alkylating agent
Highly reactive chemical that introduces alkyl radicals into biologically active molecules and thereby prevents their proper functioning. It could be used as an antineoplastic agent, but it might be very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. It could also be used as a component of poison gases.
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polar aprotic solvent
A solvent with a comparatively high relative permittivity (or dielectric constant), greater than ca. 15, and a sizable permanent dipole moment, that cannot donate suitably labile hydrogen atoms to form strong hydrogen bonds.
non-narcotic analgesic
A drug that has principally analgesic, antipyretic and anti-inflammatory actions. Non-narcotic analgesics do not bind to opioid receptors.
antidote
Any protective agent counteracting or neutralizing the action of poisons.
MRI contrast agent
geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
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View more via ChEBI Ontology
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(methanesulfinyl)methane
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dimethyl sulfoxide
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dimethyl sulfoxide
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ChemIDplus
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dimethyli sulfoxidum
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ChemIDplus
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diméthylsulfoxyde
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ChemIDplus
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dimetil sulfóxido
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ChemIDplus
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(CH3)2SO
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NIST Chemistry WebBook
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Dimethyl sulfoxide
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KEGG COMPOUND
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DIMETHYL SULFOXIDE
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PDBeChem
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dimethyl sulfoxide
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UniProt
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dimethyl sulfur oxide
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NIST Chemistry WebBook
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dimethyl sulphoxide
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ChemIDplus
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Dimethylsulfoxid
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ChEBI
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DMSO
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KEGG COMPOUND
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dmso
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IUPAC
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methylsulfinylmethane
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ChemIDplus
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S(O)Me2
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ChEBI
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sulfinylbis(methane)
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ChemIDplus
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659
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ChemSpider
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906
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DrugCentral
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C00053120
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KNApSAcK
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c0236
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UM-BBD
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C11143
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KEGG COMPOUND
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D01043
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KEGG DRUG
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DB01093
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Dimethyl_sulfoxide
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DMS
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DMSO
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FDB000764
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HMDB0002151
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HMDB
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LSM-36361
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LINCS
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1556
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Gmelin Registry Number
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Gmelin
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506008
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Reaxys Registry Number
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Reaxys
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67-68-5
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CAS Registry Number
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KEGG COMPOUND
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67-68-5
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CAS Registry Number
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ChemIDplus
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67-68-5
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CAS Registry Number
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NIST Chemistry WebBook
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Kollerup Madsen B, Hilscher M, Zetner D, Rosenberg J (2018)
Adverse reactions of dimethyl sulfoxide in humans: a systematic review.
F1000Research 7, 1746 [PubMed:31489176]
[show Abstract]
Background: Dimethyl sulfoxide (DMSO) has been used for medical treatment and as a pharmacological agent in humans since the 1960s. Today, DMSO is used mostly for cryopreservation of stem cells, treatment of interstitial cystitis, and as a penetrating vehicle for various drugs. Many adverse reactions have been described in relation to the use of DMSO, but to our knowledge, no overview of the existing literature has been made. Our aim was to conduct a systematic review describing the adverse reactions observed in humans in relation to the use of DMSO. Methods: This systematic review was reported according to the PRISMA-harms (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. The primary outcome was any adverse reactions occurring in humans in relation to the use of DMSO. We included all original studies that reported adverse events due to the administration of DMSO, and that had a population of five or more. Results: We included a total of 109 studies. Gastrointestinal and skin reactions were the commonest reported adverse reactions to DMSO. Most reactions were transient without need for intervention. A relationship between the dose of DMSO given and the occurrence of adverse reactions was seen. Conclusions: DMSO may cause a variety of adverse reactions that are mostly transient and mild. The dose of DMSO plays an important role in the occurrence of adverse reactions. DMSO seems to be safe to use in small doses. Registration: PROSPERO CRD42018096117. | Stachura SS, Malajczuk CJ, Mancera RL (2018)
Molecular dynamics simulations of a DMSO/water mixture using the AMBER force field.
Journal of molecular modeling 24, 174 [PubMed:29938311]
[show Abstract]
Due to its protective properties of biological samples at low temperatures and under desiccation, dimethyl sulfoxide (DMSO) in aqueous solutions has been studied widely by many experimental approaches and molecular dynamics (MD) simulations. In the case of the latter, AMBER is among the most commonly used force fields for simulations of biomolecular systems; however, the parameters for DMSO published by Fox and Kollman in 1998 have only been tested for pure liquid DMSO. We have conducted an MD simulation study of DMSO in a water mixture and computed several structural and dynamical properties such as of the mean density, self-diffusion coefficient, hydrogen bonding and DMSO and water ordering. The AMBER force field of DMSO is seen to reproduce well most of the experimental properties of DMSO in water, with the mixture displaying strong and specific water ordering, as observed in experiments and multiple other MD simulations with other non-polarizable force fields. Graphical abstract Hydration structure within hydrogen-bonding distance around a DMSOmolecule. | Rawls WF, Cox L, Rovner ES (2017)
Dimethyl sulfoxide (DMSO) as intravesical therapy for interstitial cystitis/bladder pain syndrome: A review.
Neurourology and urodynamics 36, 1677-1684 [PubMed:28220525]
[show Abstract]
AimsThe purpose of this review is to update the current understanding of dimethyl sulfoxide (DMSO) and its role in the treatment of interstitial cystitis (IC).MethodsA systematic review was conducted using the PRIMSA checklist to identify published articles involving intravesical DMSO for the treatment of IC.ResultsThirteen cohort studies and three randomized-controlled trials were identified. Response rates relying on subjective measurement scores range from 61 to 95%. No increased efficacy was found with "cocktail" DMSO therapy. Great variation existed in diagnostic criteria, DMSO instillation protocols and response measurements.ConclusionsThe current evidence backing DMSO is a constellation of cohort studies and a single randomized-controlled trial versus placebo. The optimal dose, dwell time, type of IC most likely to respond to DMSO, definitions of success/failure and the number of treatments are not universally agreed upon. Improvements in study design, phenotyping patients based on symptoms, as well as the emergence of reliable biomarkers of the disease may better guide the use of DMSO in the future. | Frankowski H, Alavez S, Spilman P, Mark KA, Nelson JD, Mollahan P, Rao RV, Chen SF, Lithgow GJ, Ellerby HM (2013)
Dimethyl sulfoxide and dimethyl formamide increase lifespan of C. elegans in liquid.
Mechanisms of ageing and development 134, 69-78 [PubMed:23313473]
[show Abstract]
Lifespan extension through pharmacological intervention may provide valuable tools to understanding the mechanisms of aging and could uncover new therapeutic approaches for the treatment of age-related disease. Although the nematode Caenorhabditis elegans is well known as a particularly suitable model for genetic manipulations, it has been recently used in a number of pharmacological studies searching for compounds with anti-aging activity. These compound screens are regularly performed in amphipathic solvents like dimethyl sulfoxide (DMSO), the solvent of choice for high-throughput drug screening experiments performed throughout the world. In this work, we report that exposing C. elegans to DMSO in liquid extends lifespan up to 20%. Interestingly, another popular amphipathic solvent, dimethyl formamide (DMF), produces a robust 50% increase in lifespan. These compounds work through a mechanism independent of insulin-like signaling and dietary restriction (DR). Additionally, the mechanism does not involve an increased resistance to free radicals or heat shock suggesting that stress resistance does not play a major role in the lifespan extension elicited by these compounds. Interestingly, we found that DMSO and DMF are able to decrease the paralysis associated with amyloid-β3-42 aggregation, suggesting a role of protein homeostasis for the mechanism elicited by these molecules to increase lifespan. | Delgado-Goñi T, Martín-Sitjar J, Simões RV, Acosta M, Lope-Piedrafita S, Arús C (2013)
Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.
NMR in biomedicine 26, 173-184 [PubMed:22814967]
[show Abstract]
Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. | Song YM, Song SO, Jung YK, Kang ES, Cha BS, Lee HC, Lee BW (2012)
Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction.
Autophagy 8, 1085-1097 [PubMed:22722716]
[show Abstract]
Induction of autophagy is known not only to regulate cellular homeostasis but also to decrease triglyceride accumulation in hepatocytes. The aim of this study is to investigate whether DMSO (dimethyl sulfoxide) has a beneficial role in free fatty acid-induced hepatic fat accumulation. In HepG2 cells, treatment with 0.5 mM palmitate for six hours significantly increased lipid and triglyceride (TG) accumulation, assessed by Oil-red O staining and TG quantification assay. Treatment with 0.01% DMSO for 16 h statistically reduced palmitate-induced TG contents. Pretreatment of 10 mM 3-methyladenine (3MA) for 2 h restored hepatocellular lipid contents, which were attenuated by treatment with DMSO. DMSO increased LC3-II conversion and decreased SQSTM1/p62 expression in a time and dose-dependent manner. In addition, the number of autophagosomes and autolysosomes, as seen under an electron microscopy, as well as the percentage of RFP-LAMP1 colocalized with GFP-LC3 dots in cells transfected with both GFP-LC3 and RFP-LAMP1, as seen under a fluorescent microscopy, also increased in DMSO-treated HepG2 cells. DMSO also suppressed p-eIF2α/p-EIF2S1, ATF4, p-AKT1, p-MTOR and p-p70s6k/p-RPS6KB2 expression as assessed by western blotting. Knockdown of ATF4 expression using siRNA suppressed ATF4 expression and phosphorylation of AKT1, MTOR and RPS6KB2, but increased LC3-II conversion. DMSO reduced not only soluble but also insoluble mtHTT (mutant huntingtin aggregates) expressions, which were masked in the presence of autophagy inhibitor. DMSO, a kind of chemical chaperone, activated autophagy by suppressing ATF4 expression and might play a protective role in the development of fatty acid-induced hepatosteatosis. | Julien C, Marcouiller F, Bretteville A, El Khoury NB, Baillargeon J, Hébert SS, Planel E (2012)
Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation.
PloS one 7, e40020 [PubMed:22768202]
[show Abstract]
Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer's disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser(202)/Thr(205)), PHF-1 (Ser(396)/Ser(404)) and AT180 (Thr(231)) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro. | Capriotti K, Capriotti JA (2012)
Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology.
The Journal of clinical and aesthetic dermatology 5, 24-26 [PubMed:23050031]
[show Abstract]
Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology. | Hoang BX, Tran DM, Tran HQ, Nguyen PT, Pham TD, Dang HV, Ha TV, Tran HD, Hoang C, Luong KN, Shaw DG (2011)
Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain.
Journal of pain & palliative care pharmacotherapy 25, 19-24 [PubMed:21426213]
[show Abstract]
Pain is a major concern of cancer patients and a significant problem for therapy. Pain can become a predominant symptom in advanced cancers. In this open-label clinical study, the authors have treated 26 cancer patients who have been declared as terminal without the option of conventional treatment. These patients suffered from high levels of pain that was poorly managed by all available interventional approaches recommended by World Health Organization (WHO) guideline. The results indicate that intravenous infusion of dimethyl sulfoxide (DMSO) and sodium bicarbonate (SB) solution can be a viable, effective, and safe treatment for refractory pain in cancer patients. These patients had pain due to the disease progression and complication of chemotherapy and radiation. Moreover, the preliminary clinical outcome of 96-day follow-up suggests that the application of DMSO and SB solution intravenously could lead to better quality of life for patients with nontreatable terminal cancers. The data of this clinical observation indicates that further research and application of the DMSO and SB combination may help the development of an effective, safe, and inexpensive therapy to manage cancer pain. | Marren K (2011)
Dimethyl sulfoxide: an effective penetration enhancer for topical administration of NSAIDs.
The Physician and sportsmedicine 39, 75-82 [PubMed:22030943]
[show Abstract]
Dimethyl sulfoxide (DMSO) is a molecule with a long history in pharmaceutics and is now well established as a penetration enhancer in topical pharmaceutical formulations. It is currently used for this purpose in diclofenac sodium topical solution (approved in the United States to treat signs and symptoms of osteoarthritis) and idoxuridine topical solution (approved in Europe for the treatment of herpes zoster). This article reviews the mechanism of action of DMSO as a pharmaceutical penetration enhancer, the characteristics of the molecule that facilitate transdermal drug delivery, and studies of efficacy and safety. The clinical use of pharmaceutical-grade DMSO as a penetration enhancer is supported by the robust data that have accumulated over the past 3 decades demonstrating the favorable safety and tolerability profile. Dimethyl sulfoxide is a safe and effective mechanism for facilitating the transdermal delivery of both hydrophilic and lipophilic medications to provide localized drug delivery. | Wang X, Wang X, Li L, Wang D (2010)
Lifespan extension in Caenorhabditis elegans by DMSO is dependent on sir-2.1 and daf-16.
Biochemical and biophysical research communications 400, 613-618 [PubMed:20828537]
[show Abstract]
Dimethyl sulfoxide (DMSO) is an important solvent that is widely used in industry and medical studies, as well as in the study of aging, in which it is used as a negative control for lifespan assays; however, our data showed that 0.5% and 2% DMSO extended the lifespan of Caenorhabditis elegans by 24.4% and 23.0% (the first trial), respectively. Treatment with 0.5% DMSO did not affect the progeny number or the lifespan of C. elegans under thermal stress. Using real time reverse transcription-polymerase chain reaction (RT-PCR), we found that the expression levels of hsp-16.2, hsp-70, lys-7, old-1, and sod-5 were enhanced by 2.5, 2.9, 1.3, 2.3, and 4.5-fold, respectively, after treatment with 0.5% DMSO. This suggests that these genes downstream of DAF-16 might function in the lifespan extension properties of DMSO. Using the transgenic strain lys-7::GFP, we found that treatment with 0.5% DMSO also caused expression levels of lys-7 increased by 1.5-fold. Genetic analysis using mutants of aging-related genes showed that lifespan extension in C. elegans by DMSO was dependent on sir-2.1 and daf-16 but not eat-2 or hsf-1. In summary, we report the function and the putative mechanism of DMSO in lifespan extension of C. elegans. This study draws attention to using DMSO as a solvent when conducting aging studies. | Jacob SW, de la Torre JC (2009)
Pharmacology of dimethyl sulfoxide in cardiac and CNS damage.
Pharmacological reports : PR 61, 225-235 [PubMed:19443933]
[show Abstract]
The pharmacological effects of dimethyl sulfoxide (DMSO) administration include some desirable properties that may be useful in the treatment of medical disorders resulting in tissue injury and compromised organ systems. These properties include the reported effects of DMSO on impaired blood flow, suppression of cytotoxicity from excess glutamate release that may result in lethal NMDA-AMPA activation, restriction of cytotoxic Na(+) and Ca(2+) entry into damaged cells, blocking tissue factor (TF) from contributing to thrombosis, reduction of intracranial pressure, tissue edema, and inflammatory reactions, and inhibition of vascular smooth muscle cell migration and proliferation that can lead to atherosclerosis of the coronary, peripheral, and cerebral circulation. A review of the basic and clinical literature on the biological actions of DMSO in cardiac and central nervous system (CNS) damage or dysfunction indicates that this agent, alone or in combination with other synergistic molecules, has been reported to neutralize or attenuate pathological complications that harmed or can further harm these two organ systems. The effects of DMSO make it potentially useful in the treatment of medical disorders involving head and spinal cord injury, stroke, memory dysfunction, and ischemic heart disease. | (2009)
Dexrazoxane: new indication. Anthracycline extravasation: continue using dimethyl sulfoxide.
Prescrire international 18, 6-8 [PubMed:19382398]
[show Abstract]
1) Anthracycline extravasation can provoke extensive tissue necrosis, sometimes with serious consequences. Topical dimethylsulfoxide (DMSO) is the main antidote known to prevent this necrosis. It is used off-licence in France, based on the results of non-comparative trials. Among nearly 150 patients treated with dimethylsulfoxide, only one required surgery and about 10% of patients had sequelae; 2) A product based on dexrazoxane, an iron chelator, also approved to prevent anthracycline cardiotoxicity, has now been authorized for intravenous treatment of anthracycline extravasation; 3) Clinical evaluation of dexrazoxane in this setting does not include any trials versus dimethylsulfoxide. The combination of dexrazoxane plus dimethylsulfoxide is contraindicated, based on the results of animal studies; 4) Clinical evaluation of dexrazoxane only includes one case of anthracycline extravasation from a central venous line; 5) In two non-comparative trials in a total of 54 patients, only one patient required surgery for tissue necrosis. About one-third of patients had local complications (sensory disorders, pain, cutaneous atrophy, or restricted movement); 6) The only known adverse effect of topical dimethylsulfoxide is local irritation. In contrast, 10% of patients who received intravenous dexrazoxane had an infection that the investigators considered possibly linked to dexrazoxane. In addition to the known haematological effects of dexrazoxane (leukopenia and thrombocytopenia), other serious adverse events observed in the two trials included a major increase in hepatic transaminase activity, elevated creatinine levels, and hyper- or hypokalaemia; 7) Based on an evaluation that is neither sufficiently thorough nor rigorous, the risk-benefit balance of intravenous dexrazoxane appears to be less favourable than that of local dimethylsulfoxide, which should therefore continue to be used in this setting. In the meantime, preventive measures should be strictly followed in order to prevent extravasation from occurring. The assessment of dexrazoxane in anthracycline extravasation from a central line also remains inadequate. | Di Giorgio AM, Hou Y, Zhao X, Zhang B, Lyeth BG, Russell MJ (2008)
Dimethyl sulfoxide provides neuroprotection in a traumatic brain injury model.
Restorative neurology and neuroscience 26, 501-507 [PubMed:19096138]
[show Abstract]
PurposeThe objective of this study was to evaluate the neuroprotective potential of the antioxidant, curcumin compared to alpha-tocopherol in a rat model of traumatic brain injury (TBI).MethodsMale Sprague-Dawley rats were administered curcumin (3, 30, 300 mg/kg), alpha-tocopherol (100 mg/kg), DMSO vehicle, or saline, 30 min prior to and 30 and 90 min after moderate lateral fluid percussion TBI. Rats were euthanized at 24 hours after injury and coronal brain sections were stained with Fluoro-Jade to identify degenerating neurons. Degenerating neurons in the CA2-3 sector of the dorsal hippocampus were quantified in 10 sections spaced 300 microm apart in each rat.ResultsOne way ANOVA revealed a significant difference (p = 0.01) between groups. The curcumin, alpha-tocopherol, and DMSO groups had significantly reduced numbers of degenerating neurons compared to the saline-treated group. No significant differences were observed between any of the drug treatment groups or the DMSO group.ConclusionsSince protection in the DMSO vehicle group was equal to that of the experimental groups, no conclusions about neuroprotection regarding alpha-tocopherol or curcumin can be made from this study. The results suggest that DMSO may be acting as an overriding neuroprotectant in this experiment. We conclude that DMSO is a viable neuroprotective agent against secondary cell death in TBI. | Tomazzolli R, Serra MD, Bellisola G, Colombatti M, Guella G (2006)
A fluorescence-based assay for the reductase activity of protein disulfide isomerase.
Analytical biochemistry 350, 105-112 [PubMed:16434015]
[show Abstract]
We report on a new spectrofluorimetric assay for the measurement of reductase activity of proteins belonging to the superfamily of thioredoxins such as protein disulfide isomerase (PDI). The assay relies on the preparation of a fluorescence-quenched substrate easily accessible in two steps through functional group transformations of the peptide Gly-Cys-Asp. In the first step fluorescein isothiocyanate is linked to the Gly-NH(2) terminus and in the second step the Cys-SH groups are converted into a disulfide bond. Both intermediate and final substrate have been fully characterized by mass spectrometric and nuclear magnetic resonance measurements. Dimethyl sulfoxide is here reported to be a mild oxidizing agent allowing us to obtain in good overall yield the assay substrate in a single synthetic step. A reliable estimation of PDI reductase activity is obtained via the detection of a strong fluorescence enhancement after enzymatic reduction. Moreover, our assay provides further support for the key role played by thioredoxin reductase in enabling disulfide reductase activity of PDI. | Barnes I, Hjorth J, Mihalopoulos N (2006)
Dimethyl sulfide and dimethyl sulfoxide and their oxidation in the atmosphere.
Chemical reviews 106, 940-975 [PubMed:16522014] | Pamuk AG, Saatci I, Cekirge HS, Aypar U (2005)
A contribution to the controversy over dimethyl sulfoxide toxicity: anesthesia monitoring results in patients treated with Onyx embolization for intracranial aneurysms.
Neuroradiology 47, 380-386 [PubMed:15868171]
[show Abstract]
Onyx injection is a new technique for embolization of cerebral aneurysms that is involved in a controversy about the 'toxicity' of its solvent, dimethyl sulfoxide (DMSO). We retrospectively studied 38 patients treated for aneurysms with the liquid polymer, Onyx. Induction was with propofol, fentanyl and vecuronium, and anesthesia was maintained with isoflurane in O2 and N2O. The patients were given 500 ml of fluid after induction, and bradycardia was prevented in order to keep patients hyperdynamic. Electrocardiography (ECG), non-invasive blood pressure (NIBP), pulse oximetry, core temperatures, invasive blood pressure (BP), etCO2, and urine output were monitored throughout the intervention. Heart rate and BP changes in response to balloon inflation, DMSO injection, Onyx injection and balloon deflation were recorded. The patients were followed with serial neurological examinations, computerized tomography and/or magnetic resonance imaging postoperatively for evidence of any neurological injury. Cumulative DMSO doses were always well under previously implicated doses for systemic toxicity. No changes implicating toxic reactions were observed during DMSO and Onyx injections. Balloon-induced changes returned to baseline within 1 min of balloon deflation. Technique-related permanent morbidity occurred in two patients (worsening of cranial nerve palsies in one and monocular blindness in another) and intracranial hemorrhage with resulting death in one patient. All patients showed a tendency to oxygen desaturation, but this finding did not cause any clinical consequence. Anesthesiologists need to be vigilant in monitoring patients treated with techniques that are new or are being developed. We have seen no evidence of toxicity or any anesthetic complications in our group of patients, our only clinical concern being a tendency to oxygen desaturation, which may be explained by the inhalational elimination of DMSO. | Hopkins JE, Naisbitt DJ, Humphreys N, Dearman RJ, Kimber I, Park BK (2005)
Exposure of mice to the nitroso metabolite of sulfamethoxazole stimulates interleukin 5 production by CD4+ T-cells.
Toxicology 206, 221-231 [PubMed:15588915]
[show Abstract]
Sulfamethoxazole hypersensitivity may be caused by production of the protein-reactive metabolite nitroso sulfamethoxazole (SMX-NO) and interaction of SMX-NO with T-cells. We have characterised the nature of the immune response induced by administration of sulfamethoxazole, sulfamethoxazole metabolites and nitrosobenzene to BALB/c mice. Drugs were administered over a 13-day period to induce polarised cytokine secretion profiles. Proliferation was measured by [(3)H] thymidine incorporation. Cytokine secretion was monitored by ELISA. Results were compared with those provoked by exposure to type 1 and type 2 chemical allergens, 2,4-dinitrochlorobenzene (DNCB) and trimellitic anhydride (TMA). CD4(+) or CD8(+) T-cells were depleted ex vivo to identify the primary source of cytokines. Lymph node activation was observed following treatment with DNCB, TMA, nitrosobenzene and SMX-NO, but not with sulfamethoxazole or sulfamethoxazole hydroxylamine (SMX-NHOH). DNCB and TMA induced type 1 and type 2 cytokine profiles, respectively. SMX-NO treatment stimulated the production of high levels of IL-5, variable amounts of IFN-gamma, and relatively low levels of IL-10 and IL-4. Nitrosobenzene-activated lymph node cells secreted only low levels of IFN-gamma and IL-5. Depletion of CD4(+) or CD8(+) T-cells from SMX-NO stimulated lymph node cells revealed that CD4(+) T-cells were the major source of IL-5. In conclusion, the data presented indicates that subcutaneous administration to mice of SMX-NO, but not the parent drug, stimulated the secretion of high levels of IL-5 from activated CD4(+) T-cells, which is consistent with the clinical profile of the drug. | Nogler-Semenitz E, Mader I, Fürst-Weger P, Terkola R, Wassertheurer S, Giovanoli P, Mader RM (2004)
[Extravasation of cytotoxic agents].
Wiener klinische Wochenschrift 116, 289-295 [PubMed:15237653]
[show Abstract]
A variety of antineoplastic agents is associated with toxicity to healthy tissue and therefore represents a hazard for patients in case of extravasation. The most common risk factors include patient associated and iatrogenic risk factors. Due to the possible complications after extravasation, the knowledge of these risk factors is the basis for prevention, which is of utmost importance. A classification of antineoplastic agents according to the type of tissue damage includes the categories vesicant, irritant, and non-vesicant. Dependent on the extravasated agent, a series of emergency measures should be considered, preferably adhering to a standard operation procedure. There is good evidence for the successful use of antidotes to some antineoplastic agents. These antidotes are dimethylsulfoxide or hyaluronidase, often combined with topical measures such as cooling or application of heat. The application of sodium bicarbonate, sodium thiosulfate, and heparin is not recommended, whereas the usefulness of corticosteroids is still a matter of controversial discussions. Ambiguity in the management of extravasation is often a consequence of limited clinical evidence. Due to our deficient knowledge about some of the administered cytotoxics, there is ongoing need for action even after decades of therapy with antineoplastic agents. | Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003)
Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects.
Biochemical pharmacology 65, 1035-1041 [PubMed:12663039]
[show Abstract]
DMSO is an amphipathic molecule with a highly polar domain and two apolar methyl groups, making it soluble in both aqueous and organic media. It is one of the most common solvents for the in vivo administration of several water-insoluble substances. Despite being frequently used as a solvent in biological studies and as a vehicle for drug therapy, the side-effects of DMSO (undesirable for these purposes) are apparent from its utilization in the laboratory (both in vivo and in vitro) and in clinical settings. DMSO is a hydrogen-bound disrupter, cell-differentiating agent, hydroxyl radical scavenger, intercellular electrical uncoupler, intracellular low-density lipoprotein-derived cholesterol mobilizing agent, cryoprotectant, solubilizing agent used in sample preparation for electron microscopy, antidote to the extravasation of vesicant anticancer agents, and topical analgesic. Additionally, it is used in the treatment of brain edema, amyloidosis, interstitial cystitis, and schizophrenia. Several systemic side-effects from the use of DMSO have been reported, namely nausea, vomiting, diarrhea, hemolysis, rashes, renal failure, hypertension, bradycardia, heart block, pulmonary edema, cardiac arrest, and bronchospasm. Looking at the multitude of effects of DMSO brought to light by these studies, it is easily understood how many researchers working with DMSO (or studying one of its specific effects) might not be fully aware of the experiences of other groups who are working with it but in a different context. | Naisbitt DJ, Gordon SF, Pirmohamed M, Burkhart C, Cribb AE, Pichler WJ, Park BK (2001)
Antigenicity and immunogenicity of sulphamethoxazole: demonstration of metabolism-dependent haptenation and T-cell proliferation in vivo.
British journal of pharmacology 133, 295-305 [PubMed:11350866]
[show Abstract]
Sulphamethoxazole has been associated with the occurrence of hypersensitivity reactions. There is controversy as to whether the immune response is metabolism-dependent or -independent. We have therefore investigated the site of antigen formation and the nature of the drug signal presented to the immune system in vivo. Male Wistar rats were dosed with sulphamethoxazole, sulphamethoxazole hydroxylamine or nitroso sulphamethoxazole. Antigen formation on cell surfaces was determined by flow cytometry using a specific anti-sulphamethoxazole antibody. Immunogenicity was determined by assessment of ex vivo T-cell proliferation. Administration of nitroso sulphamethoxazole, but not sulphamethoxazole or sulphamethoxazole hydroxylamine, resulted in antigen formation on the surface of lymphocytes, splenocytes and epidermal keratinocytes, and a strong proliferative response of splenocytes on re-stimulation with nitroso sulphamethoxazole. Rats dosed with sulphamethoxazole or sulphamethoxazole hydroxylamine did not respond to any of the test compounds. CD4+ or CD8+ depleted cells responded equally to nitroso sulphamethoxazole. The proliferative response to nitroso sulphamethoxazole was seen even after pulsing for only 5 min, and was not inhibited by glutathione. Responding cells produced IFN-gamma, but not IL-4. Haptenation of cells by sulphamethoxazole hydroxylamine was seen after depletion of glutathione by pre-treating the rats with diethyl maleate. Splenocytes from the glutathione-depleted sulphamethoxazole hydroxylamine-treated rats responded weakly to nitroso sulphamethoxazole, but not to sulphamethoxazole or sulphamethoxazole hydroxylamine. Dosing of rats with sulphamethoxazole produced a cellular response to nitroso sulphamethoxazole (but not to sulphamethoxazole or its hydroxylamine) when the animals were primed with complete Freund's adjuvant. These studies demonstrate the antigenicity of nitroso sulphamethoxazole in vivo and provide evidence for the role of drug metabolism and cell surface haptenation in the induction of a cellular immune response in the rat. | Chang CK, Albarillo MV, Schumer W (2001)
Therapeutic effect of dimethyl sulfoxide on ICAM-1 gene expression and activation of NF-kappaB and AP-1 in septic rats.
The Journal of surgical research 95, 181-187 [PubMed:11162043]
[show Abstract]
BackgroundDimethyl sulfoxide (DMSO) is a potent antioxidant which protects against endotoxemia and septic shock in animal models. We investigated the therapeutic effect of DMSO on intercellular adhesion molecule 1 (ICAM-1) gene expression and activation of nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) in a rat model of peritonitis sepsis. This postchallenge model simulates the clinical treatment of ruptured viscus peritonitis.Materials and methodsPeritonitis was produced by subjecting rats to laparotomy, followed by a 1-cm cecal incision (CI) to produce fecal soilage of the peritoneum. Rats were subjected to laparotomy only for the sham-operated group. For the protection study, DMSO (6 ml/kg) was injected ip at 30, 60, or 90 min post-CI surgery. The levels of ICAM-1 mRNA expression and activation of NF-kappaB and AP-1 in livers were determined at 3 and 6 h post-CI.ResultsAt 3 h post-CI surgery (early sepsis), DMSO treatment at 30 and 60 min post-CI surgery significantly inhibited sepsis-induced ICAM-1 mRNA expression and activation of NF-kappaB and AP-1. DMSO has no effect on ICAM-1 gene expression and activation of NF-kappaB and AP-1 when administered at 90 min post-CI surgery. At 6 h post-CI surgery (late sepsis), DMSO administered at 30, 60, or 90 min post-CI surgery significantly inhibited ICAM-1 mRNA expression and NF-kappaB activation but not AP-1 activation.ConclusionsTherapeutic treatment of DMSO inhibited sepsis-induced activation of NF-kappaB and AP-1, resulting in the suppression of ICAM-1 gene expression in the livers of peritonitis septic rats. This finding suggests that reactive oxidants are involved in the signal transduction pathways for activation of NF-kappaB and AP-1. Thus, antioxidants which inhibit NF-kappaB and AP-1 activation may be beneficial in treating sepsis and septic shock. | Ali BH (2001)
Dimethyl sulfoxide: recent pharmacological and toxicological research.
Veterinary and human toxicology 43, 228-231 [PubMed:11474739]
[show Abstract]
A survey of the literature published in the past 2 decades on the basic pharmacology, therapeutic uses and toxicity of dimethyl sulfoxide (DMSO) is presented. A salient pharmacological action of DMSO is its ability to scavenge oxygen-free radicals implicated in xenobiotic-induced tissue damages when given before, during or several hours after the tissue insult. More trials with DMSO in diseases and conditions caused by oxygen-free radicals are warranted. | Brayton CF (1986)
Dimethyl sulfoxide (DMSO): a review.
The Cornell veterinarian 76, 61-90 [PubMed:3510103]
[show Abstract]
Dimethyl sulfoxide (DMSO) is a very simple compound that has stimulated much controversy in the scientific and popular literature. Fig. 1 It is an aprotic solvent. Therapeutic and toxic agents that are not soluble in water are often soluble in DMSO. DMSO has a very strong affinity for water; on exposure to air, pure DMSO is rapidly diluted. DMSO's physiologic and pharmacologic properties and effects are incompletely understood. Properties that are considered to be particularly important to its therapeutic and toxic effects include: its own rapid penetration and enhanced penetration of other substances across biologic membranes; free radical scavenging; effects on coagulation; anticholinesterase activity; and DMSO-induced histamine release by mast cells. DMSO's systemic toxicity is considered to be low. Combinations of DMSO with other toxic agents probably constitute its greatest toxic potential. The scientific literature is reviewed with particular attention to mechanisms underlying DMSO's reported therapeutic and toxic effects. Currently approved, veterinary applications of DMSO are limited. DMSO's potential value in specific, approved and unapproved veterinary applications is discussed. | Swanson BN (1985)
Medical use of dimethyl sulfoxide (DMSO).
Reviews in clinical & basic pharmacology 5, 1-33 [PubMed:3916302]
[show Abstract]
DMSO is a clear odorless liquid, inexpensively produced as a by-product of the paper industry. It is widely available in the USA as a solvent but its medical use is currently restricted by the FDA to the palliative treatment of interstitial cystitis and to certain experimental applications. Cutaneous manifestations of scleroderma appear to resolve (albeit equivocally) following topical applications of high concentrations of DMSO. A limited number of small clinical trials indicate that intravenous DMSO may be of benefit in the treatment of amyloidosis, possibly by mobilizing amyloid deposits out of tissues into urine. Dermal application of DMSO seems to provide rapid, temporary, relief of pain in patients with arthritis and connective tissue injuries. However, claims for antiinflammatory effects or acceleration of healing are currently unwarranted. There is no evidence that DMSO can alter progression of degenerative joint disease, and, for this reason, DMSO may be considered for palliative treatment only and not to the exclusion of standard antiinflammatory agents. The safety of DMSO in combination with other drugs has not been established; neurotoxic interactions with sulindac have been reported. In experimental animals, intravenous DMSO is as effective as mannitol and dexamethasone in reversing cerebral edema and intracranial hypertension. An initial clinical trial in 11 patients tends to support this latter application. DMSO enhances diffusion of other chemicals through the skin, and, for this reason, mixtures of idoxuridine and DMSO are used for topical treatment of herpes zoster in the UK. Adverse reactions to DMSO are common, but are usually minor and related to the concentration of DMSO in the medication solution. Consequently, the most frequent side effects, such as skin rash and pruritus after dermal application, intravascular hemolysis after intravenous infusion and gastrointestinal discomfort after oral administration, can be avoided in large part by employing more dilute solutions. Most clinical trials of DMSO have not incorporated the components of experimental design necessary for objective, statistical evaluation of efficacy. Randomized comparisons between DMSO, placebo and known active treatments were rarely completed. Final approval of topical DMSO for treatment of rheumatic diseases in particular will require a multi-center, randomized comparison between high and low concentrations of DMSO and an orally-active, nonsteroidal antiinflammatory agent.(ABSTRACT TRUNCATED AT 400 WORDS) | Trice JM, Pinals RS (1985)
Dimethyl sulfoxide: a review of its use in the rheumatic disorders.
Seminars in arthritis and rheumatism 15, 45-60 [PubMed:3898376] | Willhite CC, Katz PI (1984)
Toxicology updates. Dimethyl sulfoxide.
Journal of applied toxicology : JAT 4, 155-160 [PubMed:6379027] | Shlafer M (1983)
Cardiac pharmacology of dimethyl sulfoxide and its postulated relevance to organ preservation in ischemic or hypoxic states.
Annals of the New York Academy of Sciences 411, 170-179 [PubMed:6309056] | Murdoch L (1982)
Dimethyl sulfoxide (DMSO)--an overview.
The Canadian journal of hospital pharmacy 35, 79-85 [PubMed:10298633]
[show Abstract]
The solvent dimethyl sulfoxide (DMSO) has received intense lay publicity sporadically over the last two decades. The compound has been particularly promoted as an analgesic and anti-inflammatory agent. Its membrane penetrant-carrier properties have also been of prime interest. The history, physical/chemical and pharmacological properties, pharmacokinetics, clinical trials, therapeutic uses, side effects and dosage/administration of DMSO are reviewed. Legal implications and concerns with regard to DMSO use are presented in addition to advice for patients. | David NA (1972)
The pharmacology of dimethyl sulfoxide.
Annual review of pharmacology 12, 353-374 [PubMed:4556944] | Martin D, Weise A, Niclas HJ (1967)
The solvent dimethyl sulfoxide.
Angewandte Chemie (International ed. in English) 6, 318-334 [PubMed:4963226] | Pope DC, Oliver WT (1966)
Dimethyl sulfoxide (DMSO).
Canadian journal of comparative medicine and veterinary science 30, 3-8 [PubMed:4223708] |
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