ISBN: 978-1-4987-1467-9
9 781498 71467990000K25303
Dimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
STANLEY W. JACOB
JACK C. DE LA TORRE
JACOB • DE LA TORRE
CHEMISTRY
First isolated as a chemical compound by a Russian chemist in 1866,  
dimethyl sulfoxide (DMSO) proved to be a near-perfect solvent for  
decades before its remarkable biological and medical activities were  
discovered. DMSO is one of the most prodigious agents ever to come  
out of the world of drug development. Its wide range of biological actions 
involving plants, animals, and humans has led to the publication of tens  
of thousands of articles in the scientific literature. Dimethyl Sulfoxide (DMSO) in Trauma and Disease examines the major 
clinical uses of DMSO in humans as supported by basic evidence derived from experiments in animals, including its effects in disorders such as osteoarthritis, interstitial cystitis, gastrointestinal inflammatory changes, scleroderma, respiratory distress, myasthenia gravis, cardiac disease, traumatic brain injury, and Alzheimer’s disease. The effects of DMSO on pain, cancer, stroke, and spinal cord injury are 
also discussed. The book explores how its chemical structure is able  
to react and deactivate toxic molecules generated by DNA damage, free radical formation, inflammation, oxidation, and infection. For the first time, the collective data on the biological, chemical, and medical actions of DMSO are presented and analyzed from the published scientific literature. Clearly written, the book incorporates easy-to-understand scientific  
descriptions that appeal both to health care professionals and the  
millions of people worldwide who have used DMSO for an assortment of 
ailments as a prescriptive or off-label medication.Dimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
K25303_Cover_PubGr.indd   All Pages 2/11/15   2:38 PMDimethyl Sulfoxide  
(DMSO) in Trauma  
and DiseaseDimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
STANLEY W. JACOB
JACK C. DE LA TORRECRC Press
Taylor & Francis Group6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742
© 2015 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20150209
International Standard Book Number-13: 978-1-4987-1468-6 (eBook - PDF)This book contains information obtained from authentic and highly regarded sources. Reasonable 
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Contents
Foreword  ................................................................................................................... ix
Authors  ...................................................................................................................... xi
Introduction  ............................................................................................................ xiii
Chapter 1 Chemistry of DMSO  ............................................................................ 1
Chemical Structure and Properties of DMSO  ..................................... 1
DMSO Solvation and Chemical Activity  ............................................. 3
Protein Folding  ..................................................................................... 4
Permeability Enhancement  .................................................................. 4
DMSO as a Chemical Chaperone  ........................................................ 5
DMSO as an Electrolyte  ....................................................................... 8
Cryoprotection  ...................................................................................... 9
DMSO in the Sea and the Atmosphere  .............................................. 10
References  .......................................................................................... 11
Chapter 2 DMSO in Basic Pharmacology  .......................................................... 15
Absorption, Fate, and Excretion of DMSO  ........................................ 15
Penetration  .......................................................................................... 16
Chemical Chaperones  ........................................................................ 16
DMSO as a Pain Medication  .............................................................. 17
Anti-Inflammatory  ............................................................................. 21
Prostaglandins  .................................................................................... 21
Cardiac Disease  .................................................................................. 24
Ulcerative Colitis  ................................................................................ 28
Skin Penetrant  .................................................................................... 29
Wound Healing  ................................................................................... 29
Burns and Scar Tissue  ........................................................................ 30
Respiratory Stimulation  ..................................................................... 32
Acute Respiratory Distress Syndrome  ............................................... 33
Experimental Blunt Chest Trauma  ..................................................... 34
Autophagy  .......................................................................................... 35
Diuresis  ............................................................................................... 36
Cholinesterase Inhibition  ................................................................... 36
Solvent Action  .................................................................................... 37
Veterinary Uses  .................................................................................. 37
Teratology and LD50 ........................................................................... 38
Ocular Effects ..................................................................................... 39
Intrawound Administration of DMSO  ............................................... 40
References  .......................................................................................... 40vi Contents
Chapter 3 DMSO Clinical Pharmacology  .......................................................... 49
DMSO in Disease  ............................................................................... 49
Pain ..................................................................................................... 50
Interstitial Cystitis  .............................................................................. 59
Gastrointestinal Disorders  .................................................................. 61
Autoimmune Disorders  ...................................................................... 61
Respiration  ......................................................................................... 62
Amyloidosis and Scleroderma  ............................................................ 62
Thromboembolic Events  .................................................................... 63
Platelet Deaggregation and Free Radical Scavenging  ........................ 66
Tissue Factor and Inflammation  ......................................................... 68
Clinical Toxicology  ............................................................................ 70
References  .......................................................................................... 71
Chapter 4 DMSO in Genetics  ............................................................................. 81
Protection from Ionizing Radiation  ................................................... 81
DMSO Protection of Single- and Double-Stranded DNA Breaks  .....83
DMSO in Cellular Differentiation ...................................................... 88
Cancer Stem Cells and Differentiation  .............................................. 92
References  .......................................................................................... 93
Chapter 5 DMSO in Basic Microbiology  ............................................................ 99
DMSO in Bacterial Infections  ............................................................ 99
Era of Antimicrobials  .................................................................... 99
DMSO and Pathogens  ...................................................................... 101
DMSO in Viral and Fungal Pathology  ............................................. 108
References  ........................................................................................ 111
Chapter 6 DMSO in Clinical Microbiology  ...................................................... 115
How Bacteria Achieve Antibiotic Resistance ................................... 115
DMSO in Multidrug-Resistant Tuberculosis  .................................... 116
References  ........................................................................................ 121
Chapter 7 DMSO in Malignancy  ...................................................................... 123
DMSO and Neoplasia  ....................................................................... 123
Friend Leukemia Cells  ..................................................................... 123
HL-60 Human Cell Line  .................................................................. 124
Metastatic Liver Disease  .................................................................. 125
DMSO Combined with Anticancer Agents  ...................................... 126
DMSO in Extravasation  ................................................................... 127vii Contents
Cancer and Radiation  ....................................................................... 127
Onyx Embolization  .......................................................................... 128
References  ........................................................................................ 129
Chapter 8 DMSO in Basic Neuroprotection  ..................................................... 133
Brain Trauma Overview  ................................................................... 133
Secondary Injury and Ischemic Penumbral Neurons  ....................... 135
DMSO in Experimental Brain Trauma  ............................................ 137
Free Radicals in Brain Injury  ........................................................... 144
Cerebral Hemodynamic Function in Brain Injury  ........................... 146
Prostaglandins  .................................................................................. 148
Tissue Factor  .................................................................................... 151
Cerebral Blood Flow  ........................................................................ 153
Concussions  ...................................................................................... 154
DMSO in Brain Concussion  ............................................................. 157
DMSO Combined with a Glycolytic Intermediate  ........................... 157
DMSO in Experimental Brain Ischemia  .......................................... 160
Ethical Considerations for Using Nonhuman Primates 
in CNS Injuries  ................................................................................. 163
Role of DMSO in Experimental Stroke  ........................................... 164
DMSO in Missile Injury to the Brain ............................................... 172
DMSO Compared to Mannitol in Missile Injury  ............................. 176
DMSO in Aging Research  ................................................................ 176
DMSO in Experimental Dementia  ................................................... 178
DMSO in Experimental Spinal Cord Injury  .................................... 182
DMSO as a Solvent  .......................................................................... 187
References  ........................................................................................ 188
Chapter 9 DMSO in Clinical Neuroprotection  ................................................. 203
Overview of Clinical Traumatic Brain Injury  .................................. 203
Head Injury in Children  ................................................................... 207
Cost and Consequences of Traumatic Brain Injury  ......................... 207
Chronic Traumatic Encephalopathy  ................................................. 208
Treating Traumatic Brain Injury  ...................................................... 209
DMSO in Traumatic Brain Injury  .................................................... 211
Optimal DMSO Dose for Traumatic Brain Injury  ........................... 214
Comparing DMSO Doses, Duration of Treatment, and Use as a First- or Second-Line Treatment for Traumatic Brain Injury
 .......... 216
DMSO in Intracranial Aneurysm Hemorrhage  ................................ 221
DMSO Compared to Progesterone for Traumatic Brain Injury  .......224
DMSO + Fructose-1,6-Disphosphate (FDP) for Ischemic Stroke  ....227
References  ........................................................................................ 231ix
Foreword
I have personally known Dr. Stanley W. Jacob and Dr. Jack C. de la Torre over a 
period of many years. My first encounter with Dr. Jacob occurred when I was a surgi -
cal intern at the Boston City Hospital, Boston, Massachusetts. It was my first month as an intern working in the emergency room when Dr. Jacob seemingly appeared out of nowhere. I was treating a patient, and he began to drill me with questions as to what I was doing and for what reasons. At the time, I believed he was a presumptu-ous medical resident from another service trying to show off his knowledge at my expense and so I told him to “shove off.” Dr. Jacob, in his neatly starched white lab coat, looked at me and softly asked, “Do you know who I am?” and then proceeded to inform me that he was the chief resident in the Harvard Surgical Service, a position revered by all who were training in surgery in Boston. I immediately apologized and told him anything he could teach me would be most welcome. Dr. Jacob and I have shared a good laugh over the years recalling this amusing case of mistaken identity. I was introduced to dimethylsulfoxide, also known as DMSO, by Dr. de la Torre 
many years ago, who told me of the unusual properties of this drug in central nervous system injuries. I have since used DMSO successfully in my research on spinal cord trauma. Drs. Jacob and de la Torre have written a book that encompasses the extensive 
and unique biological actions of DMSO, a drug that was first synthesized in 1866, when it became an important and ubiquitous solvent in most chemistry laborato -
ries. Although the multiple uses of DMSO have been explored and reported over the past half century, this book explains and discusses the diverse areas of research and therapy that have been generated directly and indirectly by the use of DMSO. The book is filled with insights on the physiological and biochemical actions of DMSO in mammalian tissue and presents a highly accurate account of these actions using evidence-based research derived from thousands of studies performed by scientists around the world. One must wonder if many in the medical community are aware of DMSO’s potential as a treatment for a number of medical problems. The clinical possibilities of DMSO were revealed in 1964, when a chemist 
observed to Dr. Jacob that after DMSO had touched his skin, he rapidly felt a garlic-like taste on his tongue. Although many individuals over the years may have had the same experience when handling DMSO, it was Dr. Jacob who realized that after contact with the chemist’s skin, the DMSO must have penetrated his dermis and entered his bloodstream with rapid transportation to his tongue. This observation led to years of study of the cell biology of DMSO and its potential for clinical uses, which has resulted in the publication of thousands of scientific and medical papers. Dr. de la Torre’s reporting on the basic and clinical uses of DMSO for traumatic 
brain injuries, stroke, and dementia is compelling, especially regarding the favorable 
effects of the drug for decreasing intracranial pressure, increasing cerebral blood 
flow, and stabilizing respiration. x Foreword
The chapters of the book are organized to introduce the reader to the structure 
and chemical actions of DMSO followed by its basic and clinical pharmacology and 
medical actions on pain, inflammatory disorders, infection, DNA damage, cancer, stroke, brain trauma, and spinal cord injury. A substantial number of references lend support to the evidence presented. Drs. Jacob and de la Torre are renowned investigators in their respective fields, 
surgery and neuroscience, and have devoted large portions of their academic lives to the study of DMSO. These authors have produced the first evidence-based collec -
tion of data on this unusual molecule. It is reasonable to expect that this book will become a standard reference on DMSO and that readers will refer to it in the future for research and treatment of a host of clinical conditions that may be improved with the use of this drug. Although the book is aimed at professionals in the health-care system, it should appeal to lay readers who have used DMSO as an off-label medication. Harry S. Goldsmith, MD, FACS
Clinical Professor of Neurological Surgery
University of California, Davis
Davis, Californiaxi
Authors
Dr. Stanley W. Jacob, MD , is the discoverer of 
the  medicinal properties of dimethylsulfoxide 
(DMSO). This discovery has led to more than 20,000 publications in such areas as pain, inflam -
mation, scleroderma, interstitial cystitis, arthritis, resistant tuberculosis, cancer, cryobiology, free radicals, stroke, and neuroprotection. Dr. Jacob received his MD from Ohio State University and completed his surgical training at Beth Israel Hospital in Boston. He was chief resident in sur -
gery at Harvard Surgical Services and instructor in 
surgery at Harvard School of Medicine before he was appointed to the faculty at Oregon Health Sciences University, where he became director of the Organ Transplant Program and later rose to the rank of Gerlinger professor of surgery. Dr. Jacob received many honors during his career, mainly for his research on DMSO, including the Kemper Foundation Research Scholar, Markle Scholar in Medical Sciences, Governor’s Award for Outstanding Northwest Scientist, and Humanitarian of the Year from the National Health Foundation. Dr. Jacob has chaired or cochaired 16 international research conferences on 
DMSO held throughout the world. He is the author of a dozen medical textbooks including the classics Elements of Anatomy and Physiology (WB Saunders, 1989)  
and Structure and Function in Man (WB Saunders, 1978). His publication list 
includes more than 170 peer-reviewed articles, dozens of book chapters, and entries in the Encyclopaedia Britannica. Dr. Jacob is presently professor emeritus of sur -
gery at the Oregon Health Sciences University. Dr. Stanley Jacob passed away on January 17, 2015. His legacy lives on. Jack C. de la Torre, MD, PhD , began his work on 
dimethylsulfoxide (DMSO) in the early 1970s shortly after his appointment as assistant professor in neurosurgery at the University of Chicago. Dr. de la Torre’s research revealed DMSO’s ability to quickly reduce intracranial pressure, restore cerebral blood flow, and stabilize respiration in nonhuman primates sustaining lethal traumatic brain injuries. For the next eight years, he extended his brain trauma findings and showed that intrave -
nous administration of DMSO was effective in 
treating primary and secondary damage following experimental ischemic stroke and spinal cord trauma. These neuroprotective properties of DMSO have been broadly confirmed by other investigators in the last three decades.xii Authors
A host of other ailments amenable to DMSO therapy were reported at the inter -
national conference “Biological Actions and Medical Applications of Dimethyl 
Sulfoxide” in 1983, chaired by Dr. de la Torre and sponsored by the New York Academy of Sciences. Besides his first faculty appointment at the University of Chicago, Dr. de la Torre 
has held professorial appointments in neurosurgery and neuroscience at Northwestern University in Chicago, the University of Ottawa, Canada, and Case Western University in Cleveland. He was visiting professor at the University of California, San Diego, University of Valencia, Spain, and the Laboratoire de Physiopathologie Cerebrovasculaire, Paris, France. Dr. de la Torre has published more than 180 peer-reviewed research articles and has written or edited a dozen medical texts on pathology, neurotransmitters, and Alzheimer’s disease. Dr. de la Torre’s training in neuroanatomy and neuropathology has led him to specialize in disorders of the brain, including stroke, cerebral trauma, and dementia. He continues his research as an adjunct professor of psychology at The University of Texas in Austin.xiii
Introduction
First isolated as a peculiar chemical compound by the Russian chemist Alexander 
Saytzeff in 1866, dimethylsulfoxide (DMSO) first proved to be a near-perfect solvent for decades until its other remarkable attributes became known to researchers and to millions of people around the planet. DMSO is one of the most remarkable agents ever to come out of the world of 
drug development. Its wide range of biological actions involving plants, animals, and humans has led to tens of thousands of articles written in the scientific literature from all parts of the planet since its medicinal discovery in 1964 by Jacob and Hershler. 1 
These investigators first pointed out DMSO’s clinical applications and, in so doing, opened a Pandora’s box of medical and scientific research into the alleviation of dis -
ease, pain, and trauma. The earliest and most impressive observation made by Jacob 
and Hershler1 was the ability of DMSO to penetrate the skin without damaging it. A few drops of DMSO spilled on the skin would quickly cause a distinctive garlic 
taste on the tongue, indicating its immediate transcutaneous penetration into the circulation. This fact alone placed DMSO in the exclusive club where small mol -
ecules (under 500 Da) can cross the integument and be considered in the possible realm of topical dermatotherapy. In later years, DMSO was tested intravenously and was shown to exert rapid and safe activity as a neuroprotective agent against various types of trauma in animals and humans. With a team of collaborators, Jacob’s initial article and others that followed 
described the effects of DMSO on pain, anti-inflammation, vasodilation, reduction of scar tissue, and antimicrobial activity, including its killing action against tubercu -
losis-resistant bacilli. These findings have led to a steady cascade of scientific papers on both in vitro  
and in vivo  systems that continue to the present time. Also, several dozen interna -
tional conferences have been held where investigators have reported the properties of DMSO on the biochemical, molecular, physiological, pharmacological, and medical systems linked to trauma and disease. This book examines the major clinical uses of DMSO in humans as supported 
by basic evidence derived from experiments in animals, including its effects as a powerful pain reliever, and in disorders such as osteoarthritis, interstitial cystitis, gastrointestinal inflammatory changes, scleroderma, respiratory distress, myasthe -
nia gravis, cardiac disease, traumatic brain injury, stroke, Alzheimer’s disease, and spinal cord trauma. In the case of DMSO, how does one categorize an agent with such a wide range of 
biological and pharmacological activities? Can one small and simple molecule affect these medical conditions in a beneficial manner? And if so, what mechanisms are at play in these processes? In order to explore the pharmacotherapeutic actions of DMSO on diverse medical 
conditions, the book offers a critical analysis of the scientific research that examined DMSO’s action as a free radical scavenger; an anti-inflammatory, antipain, anticancer, xiv Introduction
cell membrane stabilizer; and aneuroprotective agent in preventing and treating 
trauma and disease. The ability of DMSO to act as a chemical chaperone and to enhance the penetra -
tion of an accompanying compound applied topically on the skin has opened the door to the field of drug delivery by percutaneous transport of selective molecules. The book explores how the chemical structure of DMSO is able to react and deac -
tivate toxic molecules generated by DNA damage, free radical formation, inflam -
mation, infection, and tissue injury. Many toxic and potentially lethal molecules suppressed by DMSO include chemokines, interleukins, tumor necrosis factor, thromboxane, tissue factor, thrombin, and glutamate excitotoxicity. Many of these toxic molecules appear as a secondary reaction to traumatic inju-
ries and countless of disorders to overwhelm the clinical picture and disease out -
come. For this reason, the biological actions and therapeutic usefulness of DMSO have been barely scratched on the surface despite thousands of articles indicating its clinical potential. We hope this book will serve as a guide to explain the many facets of how DMSO 
works and to open new doors in the search for better ways to help the ill and the suffering. This book will be of interest to health-care workers, clinicians, basic scientists, 
and health-conscious consumers who wish to know more about the biological diver -
sity and medical applications of DMSO. REFERENCE
 1. Jacob SW, Bischel M, Hershler RJ. Dimethyl sulfoxide (DMSO): A new concept in 
pharmacotherapy. Curr Ther Res Clin Exp. 1964; Feb;6:134–135.1
1Chemistry of DMSO
CHEMICAL STRUCTURE AND PROPERTIES OF DMSO
Dimethyl sulfoxide (DMSO) was first synthesized in 1866, and the finding was 
reported a year later by the Russian organic chemist Alexander Saytzeff.1 Other 
common names of DMSO are methyl sulfoxide and methylsulfinylmethane. A sulf -
oxide is a chemical compound containing a sulfinyl functional group  attached to two 
carbon atoms. The DMSO molecule has a pyramidal structure containing sulfur, oxygen, and carbon atoms. The sulfur atom is in the center, while the two methyl groups, the oxygen atom, and a nonbonding electron pair are located at the corners (Figure 1.1). The sulfur atom serves as the positive dipole and activates the hydrogen atoms of the methyl groups making them weakly acidic and very resistant to removal in free radical reactions and allowing removal only by strongly basic reagents such as sodium hydride. 2
DMSO is produced as a by-product of wood pulping. Lignin, in the kraft pulping 
liquor wastes, is a polymer of unknown structure and the principal source of DMSO. DMSO synthesis is derived from dimethyl sulfide, a by-product of the manufacture of paper. Wood contains about 25%–30% lignin and sulfite waste liquors up to 6%. 3 
DMSO is commercially made available in the United States by Gaylord Chemical Corporation, which also makes the highly pure grade of DMSO for drug delivery and health-care applications. The principal impurity present in DMSO is water, and the purified solvent will 
readily absorb water vapor if exposed to the atmosphere. Solvents are classified as either polar or nonpolar, and the most common measure 
of solvent polarity is the dielectric constant. The sulfur–oxygen bond in DMSO is quite polar so that the liquid has a high 
dielectric constant. This polarity and geometry lead to considerable organization in the liquid state in which DMSO molecules are associated into chains by dipole attraction. 3 Electrophiles are atoms, molecules, and ions that behave as electron 
acceptors. Nucleophilic reagents such as DMSO behave as electron donors. The sul -
fur center in DMSO is nucleophilic toward soft electrophiles, which are molecules that readily accept electrons during a primary reaction step, while the oxygen is nucleophilic toward hard electrophiles, that is, electrons with a positive charge not easily delocalized. 4
Liquids with a high dielectric constant such as DMSO and water have a higher 
solubility of substances when immersed in a medium. For that reason, the high dielectric constant of DMSO, which is higher than most organic liquids, makes it a uniquely universal solvent
2 (Table 1.1).2 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
The presence of a liquid structure and association forces is reflected in a rather 
high freezing point, a low entropy of fusion, a high boiling point, and a high entropy 
of vaporization5 (Table 1.1). DMSO is one of the most exceptional and widely used 
solvents in organic chemistry. It is miscible with water and readily soluble in almost all organic solvents such as alcohols, esters, ketones, chlorinated solvents, and aro -
matic hydrocarbons. DMSO has been used with thousands of organic compounds to determine the quantitative strength of an acid in solution (p K
a value).2
The versatility of DMSO both as a solvent and as a reagent is partly explained by 
the dipolar nucleophilic characteristics of the molecule, which are due to the avail -
ability of free electron pairs at the oxygen or sulfur terminals. The reason is that these electrons may be shared or transferred to other protons. 6 It has been pointed 
out by Szmant6 that although DMSO is not the hydrogen donor that water is, it is 
superior to water in associations based on the induction of dipoles in aromatic rings and methylmercapto and disulfide bonds. This alteration in the configuration of immobile protein structures induced by DMSO exchanging sites with bound water molecules could explain the penetrant ability of DMSO through the skin of people and animals. 7
DMSO is an odorless, colorless, transparent, hygroscopic fluid over a wide 
range of temperatures with a slightly bitter taste. It has a low level of toxicity, and this issue is discussed in detail in the “Teratology and LD
50” section in Chapter 2. DMSO evaporates slowly at normal atmospheric pressure due to its high boiling point (189°C). At its boiling point, DMSO can decompose and has the risk of explosion. TABLE 1.1
Physical Properties of DMSO
Formula M.W. Boiling 
Point (°C) Melting 
Point (°C) Density Solubility H2O 
(g/100 g) Dielectric 
Constant Flash 
Point 
C2H6OS 78.13 189 18.4 1.092 Miscible 47 95°C
Note:  The sulfur–oxygen bond in DMSO is quite polar so that the liquid has a high dielectric constant. This polarity and geometry lead to considerable organization in the liquid state in which DMSO molecules are associated into chains by dipole attraction. See text for details. O
S
H
HHH
C
CCH3 CH3 S
O
FIGURE 1.1  (See color insert. ) Structural 3D and 2D formulas of the DMSO molecule. Sulfur (S), oxygen (O), carbon (C), and hydrogen (H).3 Chemistry of DMSO
An  explosive  reaction  can also occur when DMSO is combined with halogen 
 compounds, metal nitrides, metal perchlorates, sodium hydride, periodic acid, and flu -
orinating agents.8 When DMSO is mixed with water, considerable heat is released. The 
heat given off by DMSO mixed in water indicates that a stronger interaction between 
DMSO and water is taking place than that among DMSO molecules themselves.9
Since most chemicals used in drug formulation contain thousands of electrons, 
the behavior of these electrons in chemical reactions is hard to predict, especially as the chemical becomes more complex, because the process governing the motion of one electron depends on the motion of all the others. By contrast, DMSO is a simple molecule with only 90 electrons orbiting around their nuclei and is made up 
of 3  ca rbon, 6 hydrogen, 1 sulfur, and 1 oxygen atoms. DMSO SOLVATION AND CHEMICAL ACTIVITY
As a dipolar aprotic solvent, DMSO differs from protic solvents, such as water and alcohols, because it tends to accept rather than donate protons. 10 In chemistry, a 
protic solvent is one that has a hydrogen atom bound to an oxygen (as in a hydroxyl group) or a nitrogen (as in an amine group). The molecules of such solvents can donate a H
+ (proton). Thus, protic solvents are those that are capable of hydrogen 
bonding, which implies that they must have O–H or N–H bonds in their structure. In most cases, aprotic solvents like DMSO in various liquid media do not act as an acid or a base. 7
The most common examples of protic solvents would be water, alcohols, and 
carboxylic acids, which all have O–H bonds in their structures. Aprotic solvents, by contrast, are those that do not donate protons. These solvents, including DMSO, generally have high dielectric constants and high polarity. 11 High polarity refers to 
the polar nature of a molecule that enables it to have some interesting properties, such as being a universal solvent and possessing a high surface tension. Generally, a low-polarity solvent is said to be nonpolar if its dielectric constant is below 15. Every material has a dielectric constant, including solvents. Generally, the dielectric con -
stant of the solvent provides a rough measure of its polarity. The higher the dielectric constant, the more polar the molecule. Water, the most common solvent known, is highly polar and has a dielectric constant of 80 at 20°C, while DMSO has a dielectric constant of 47 at the same temperature and is considered a dipolar solvent. Being aprotic, DMSO can tolerate relatively strong bases and can dissolve a wide 
range of solutes while being miscible with many other solvents, a characteristic prop -
erty of polar compounds. 12
DMSO is also an amphiphilic molecule. The property of being amphiphilic refers 
to a chemical compound that possesses both hydrophilic ( water-loving ) and lipo -
philic ( fat-loving ) properties. Amphiphilic molecules display a special molecular 
structure that contains both a water-loving polar part (hydrophilic) and a water-hating nonpolar part (hydrophobic). The high polarity of DMSO allows it to dissolve many 
compounds that other solvents cannot. 5 This polar property turns out to be very 
important in determining the special structures formed by amphiphilic molecules. Amphiphiles are a special class of surface-active molecules called surfactants. They are called surface active because they have the unique properties of getting 4 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
adsorbed at various interfaces, for example, oil–water and air–water, while simul -
taneously altering the properties of the interface. The hydrophilic part of an amphi -
philic molecule is a polar molecule called the head, whereas the hydrophobic part, 
called the tail, is a hydrocarbon chain. When the fluid is water, the terms hydrophilic and hydrophobic parts can be used, respectively, to describe surfactants. Usually, surfactants are classified according to the chemical structure of their hydrophilic groups. In medicine, amphiphilic molecules such as glycolipids or sphingolipids can be found in a biological membrane having a polar water-soluble terminal group attached to a water-insoluble hydrocarbon chain. In such biological membranes, the polar parts of lipid molecules remain in water, but the hydrocarbon chains are local -
ized in the nonpolar phase. 13
PROTEIN FOLDING
The potential energy from dipole interactions is important for living organisms. The most important effect of dipole interactions on living organisms is their effect on protein folding. Every biological process involved in protein synthesis, from the binding of individual amino acids to the formation of secondary structures, tertiary structures, and even quaternary structures, is dependent on dipole–dipole inter -
actions. The dipole interaction of DMSO may be the basis of its many biological actions on living organisms. For example, the unique ability of DMSO to penetrate living tissues including the skin without causing significant damage is most likely related to its relatively polar nature, its capacity to accept hydrogen bonds, and its relatively small and compact structure. This combination of properties results in the ability of DMSO to associate with water, proteins, carbohydrates, nucleic acid, ionic substances, and other constituents of living systems. 11
DMSO is metabolized to dimethyl sulfone, which is excreted in the urine and 
feces. The other DMSO metabolite, dimethyl sulfide, is eliminated through the skin and via the breath, giving off an odor resembling garlic. 14 Dimethyl sulfide is nor -
mally present at very low levels in healthy people at concentrations less than 7 nM in blood, about 3 nM in urine, and 0.13–0.65 nM on expired breath. 15
PERMEABILITY ENHANCEMENT
The stratum corneum represents the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivering active molecules into or via the skin is to employ chemical permeability enhancers, such as DMSO. DMSO can also act as a carrier of other substances, a feature that was initially demonstrated when DMSO was topically given together with compounds such as heparin, insulin, sodium salicylate, Evans Blue dye, sulfadiazine, amino -
phylline, and thioTEPA, and these substances are found to be carried through the intact urinary bladder of the dog. 16 These findings are consistent with the experimen -
tal evidence that high concentrations of DMSO fluidize the stratum corneum lipids to enhance permeability. DMSO also promotes the lipophilic and hydrophilic penetration of many substances 
through the skin, including antiviral agents, antibiotics, and steroids. This ability of 5 Chemistry of DMSO
DMSO has led to a number of commercial preparations that combine these substances 
with DMSO for topical application.17 Skin permeation efficacy of many substances 
combined with DMSO requires a greater than 60% concentration of DMSO, which can cause wheals and erythema of the stratum corneum. 17 Following DMSO topical 
application, a mildly bitter taste can be felt on the tongue within seconds, which is quickly followed by an unpleasant odor on the breath due to dimethyl sulfide, a break -
down metabolite of DMSO. 18
DMSO AS A CHEMICAL CHAPERONE
One interesting structural property of DMSO is its action as a molecular or chemical chaperone. Chemical chaperones were first defined in the studies of mutant cystic fibrosis 
transmembrane conductance regulator proteins. 19 Chemical chaperones are small 
molecules that can nonselectively stabilize mutant proteins and have the ability in some cases to rescue protein-folding mutants within cells to assist in their folding. This feature can be very helpful in the so-called conformational or folding  diseases 
as discussed later in the text. Chemical chaperones not only aid in the folding of pro -
teins but also provide a type of quality control system  where they recognize, retain, 
and target misfolded proteins for their eventual degradation. 19
Many human diseases are known to arise as a consequence of specific point muta -
tions or deletions within genes that encode essential proteins. In many cases, these mutations and deletions do not totally destroy the biological activity of the specific gene but instead result in only subtle folding abnormalities that can lead to the newly synthesized protein being retained at the endoplasmic reticulum of the cell by the actions of the cellular quality control system. 19
For example, DMSO acting as a chemical chaperone was used in endoplasmic 
reticulum canine kidney cells expressing mutants involved in nephrogenic diabe -
tes insipidus and showed improved maturation and plasma membrane rescue.20 The 
protective action by DMSO on this model was believed to be due to an increase in the relative hydration that formed around a polypeptide, thereby inducing a tighter packing of the protein and a stabilization of the protein’s conformation. 20
Proteins are the biological workhorses that carry out the vital functions of each 
cell. Proteins exist as unfolded polypeptides or amino acid chains and derive from a sequence of messenger ribonucleic acid (mRNA) to a linear chain of amino acids. These amino acids interact with each other and, after folding, will create a 3D struc -
ture with specific and essential biological functions. If the polypeptide does not fold correctly, it will not function properly and may damage the cell. The problem with proteins is that, in some circumstances, they can become 
 misfolded , that is, folded incompletely or incorrectly. This misfolding can lead to 
serious illness because their correct molecular structure is degraded, denatured, or lost, and their specific function in the body no longer works. It has been estimated 
that about half of all human diseases are caused by protein folding defects, making 
this phenomenon a clearly important medical issue. 21
Misfolding disorders can result in neurodegenerative disorders. These disorders 
include Gaucher’s disease (misfolded beta glucocerebrosidase), Marfan syndrome 6 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
(misfolded fibrillin), Fabry’s disease (misfolded alpha galactosidase), and retinitis 
pigmentosa 3 (misfolded rhodopsin). Moreover, some cancers may be associated with misfolded proteins that become dysfunctional. One example is von Hippel Lindau disease, a dominantly inherited hereditary cancer syndrome that leads to a variety of malignant and benign tumors of the brain, spinal cord, eye, kidney, pancreas, and adrenal glands and is caused by a gene mutation that encodes the tumor suppressor protein known as pVHL. Protein misfolding disorders are not necessarily characterized by the dis -
appearance of a protein but by its deposition in insoluble aggregates within the cell. Diseases caused by protein aggregation include Alzheimer’s disease, where excessive deposits of amyloid beta and tau are found in the brain; diabetes type 2, where deposits of amylin accumulate; Parkinson’s disease, where brain deposits of α-synuclein are characteristic; and the spongiform encephalopathies such as 
Creutzfeldt–Jakob disease, described later. Hereditary transthyretin amyloidosis is caused by the aggregation of transthyretin in various tissues, such as the heart where congestive heart failure can follow or the nerves where peripheral neuropa -
thy often occurs. One of the most crucial biological activities of cells is to apply the correct folding 
of a newly produced polypeptide in the lumen of the endoplasmic reticulum of the cell into a 3D conformation or complex. Doing so ensures the stability, intracellular trafficking, and targeting of the protein to its final destination and initiation of its specific function. Protein molecules in aqueous buffer are in equilibrium between unfolded and folded states,
22 and when a protective osmolyte is added to the buffer, 
such as DMSO, there is a shift in this equilibrium toward the correct conformational shape of the protein. However, not all osmolytes are helpful in protein folding, and the most notorious in denaturing proteins is urea, a very simple molecule that is a waste product of nitrogen metabolism found normally in all our cells. Proteins that have a particularly complicated or unstable conformation sometimes 
cannot achieve their properly folded or assembled form. In these cases, other special -
ized chemical chaperones can help them return from their misfolded state to their correct folded form. It is not clear how chemical chaperones are able to nonselec -
tively stabilize the mutant proteins and facilitate their proper folding. One theory is that chemical chaperones may facilitate the proper folding of a polypeptide essen -
tially by unfolding improperly folded structures prior to their final assembly. Enzymes known as proteases can degrade those proteins that have misfolded 
incorrectly by cleaving the peptide bonds via a hydrolysis reaction. The process of protein degradation involves forming a complex with the protease, which after cleav -
age allows the released amino acids to be reused by the cell. Chemical chaperones are usually osmotically active and include, besides 
DMSO, glycerol and deuterated water. 23 These chaperones are presently being 
investigated in conformational disorders where mutations involving improper pro -
tein folding occur. Chemical chaperone research has largely focused on the central nervous system 
because of the sensitivity of this system to folding diseases. This sensitivity to pro -
tein misfolding is due to the inability of the central nervous system to regenerate itself following neuronal death.7 Chemistry of DMSO
Chemical chaperones are usually osmotically active, and this is the case with 
DMSO, glycerol, and deuterated water.23 Osmotically active compounds are known 
to be potentially useful in treating or preventing conformational disorders where 
protein folding is misguided.24
For example, Creutzfeldt–Jakob disease is a form of brain damage that can lead to 
the rapid development of increased involuntary movements and progressive  d ementia. The brain tissue develops holes much like a sponge, hence the name spongiform encephalopathy, which, like its medical name, takes on a sponge-like aspect. 24 This 
encephalopathic outcome is due to an infectious protein called prion. Prions are mis -
folded proteins that replicate by converting their properly folded counterparts into acting as a template to guide the chronic misfolding of more proteins into a prion form. 25 It is theorized that a conformational change from the normal cellular prion 
protein (PrPC) is the decisive step in the formation of the abnormal scrapie PrPSc 
isoform.26
The prion found in Creutzfeldt–Jakob disease can become quickly lethal because 
it induces refolding of native proteins into the diseased state.24 DMSO and glycerol 
have been found to revert the mutated form of the scrapie form prion (PrPSc), the 
protein responsible for the onset of prion disease,27 raising the hope of curing or 
managing Creutzfeldt–Jakob disease and other protein misfolding disorders. Although the mechanism by which PrPC is converted into PrPSc remains obscure, 
DMSO was used as a chemical chaperone and a protein-stabilizing solvent to explore the possibility of retarding the formation of PrP
Sc in scrapie-infected mouse neu -
roblastoma cells.28 It was found that DMSO proved to be effective in reducing the 
extent of PrPC conversion into its detergent insoluble form in ScN2a cells, a model of 
scrapie-infected neuroblastoma cells.28
Confirmation of these findings were reported by Shaked and his group.29 They 
showed that DMSO acted as a chemical chaperone to partially inhibit the aggrega -
tion of either PrPSc or that of its protease-resistant core, designated PrP 27–30, the 
major scrapie prion protein. From this perspective, DMSO might be useful in conformational disorders where 
protein misfolding may play an important role in the pathologic process. Such con -
formational protein disorders, as mentioned earlier, ostensibly include neurodegen -
erative disorders such as Alzheimer’s disease and Parkinson’s disease, which share some features with the prion diseases. DMSO has been used as a chemical chaperone in the autosomal neurodegen -
erative disorder Machado–Joseph disease, a type of spinocerebellar ataxia affecting muscle control and coordination of the upper and lower extremities. 30 The disease is 
caused by a gene that contains lengthy irregular repetitions of the code CAG, produc -
ing the truncated form of a mutated protein called ataxin-3. Ataxin-3 causes aggregation and cell death in vitro  and in vivo . In one in vitro 
study by Yoshida et al.,31 large intracellular aggregate bodies were remarkably 
decreased when exposed to 0.5% of DMSO. At this concentration, DMSO also sig -
nificantly suppressed neuron and non neuronal cell death frequency.31
These studies suggest that the use of DMSO in conformational disorders is an 
area of molecular research that could provide fundamental understanding of how and why proteins misfold and clues as to their eventual treatment.8 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
Due to the pleiotropic nature of DMSO, it is reasonable to assume that the struc -
tural configuration of this molecule may have the ability to target a diverse spec -
trum of pathogenic events that emerge from trauma and disease either acutely or 
chronically. This brings up the tantalizing possibility that further research into the structure of DMSO may uncover other more powerful and efficient molecules with similar molecular and chemical properties as DMSO. DMSO AS AN ELECTROLYTE
One of the more curious chemical uses found for DMSO in the last few years is as an electrolyte in rechargeable batteries. Rechargeable batteries are widely used in mod-ern society for portable consumer devices, automobile starters, electric tools, light vehicles such as electric bicycles, motorized wheelchairs, golf carts, standby genera -
tors, and large-scale electricity storage in smart or intelligent grids. The performance of rechargeable batteries depends essentially on the thermodynamics and kinetics of the electrochemical reactions involved in the components. The components are made up of an anode, cathode, electrolyte, and separator of the cells. Extensive efforts have been dedicated in the last decade to develop advanced batteries with large capacity, high energy and power density, high safety, long cycle life, fast response, and low cost. 32
Prototype lithium–oxygen (Li+–O2) batteries typically are made of a metal Li+ 
anode, a porous O2− diffusion cathode, and an organic electrolyte. DMSO has been 
proposed as an electrolyte for Li+–O2 batteries.33 Operation depends on the reduction 
of O2 at the cathode to O22−, which combines with Li+ from the electrolyte to form 
Li2O2 on discharge. The reverse reaction occurs when the battery is charging. An ideal electrolyte is considered to be one with low volatility and high oxygen 
solubility and to be inert to superoxide radicals. It was reported that an electrochemi -
cal reaction in Li2O2 batteries using a DMSO-based electrolyte was obtained and 
showed resistance of the battery after charge recovery was deemed very good when compared with that produced by fresh batteries. 34 The authors of this study con -
cluded that a superior good rate performance, reflected by a high discharge capacity and low charge potential with an optimized cathode, was observed when DMSO was used in rechargeable Li
2O2 batteries as compared with other electrolytes. These findings may open new and exciting possibilities to promote the devel -
opment of rechargeable Li–O2 batteries, especially those used to power hybrid 
and electric automobiles. However, Lithium-ion batteries for electric automobiles may not be practical due to the inadequate charging energy that is generated. Nevertheless, this shortcoming may be bridged by using rechargeable, nonaque -
ous Li–air batteries that use carbon, which is lighter and cheaper and reacts with oxygen from ambient air to produce an electric current. In fact, a lithium–air bat -
tery can safely hold 10 times more energy than the best lithium-ion batteries in the market today. New research is now being carried out where the carbon-based 
material used for the cathode is replaced with another material, containing inert 
gold nanoparticles, and with DMSO as the electrolyte that replaces the polycar -
bonates or polyethers that once served as the electrolytes. DMSO is preferred for this reaction because it is less prone to react with the cathode, is 10 times faster 9 Chemistry of DMSO
than previous Li–air batteries containing carbon cathodes, and expends much 
less power loss when the battery is charging or discharging.34
Due to its high dissolution properties and permeability, DMSO has an extensive 
application as an electronic component cleaner, as a mold release solvent for motor parts molding, and as a plant cleaning agent. DMSO can ligate metal atoms by bonding in one of two possible ways: through 
the oxygen atom or through the sulfur atom. CRYOPROTECTION
Preservation of biological materials for an extended period of time can be achieved by the process known as cryopreservation. This technique involves freezing human or animal tissues to subzero temperatures. This frozen state effectively stops chemi -
cal reactions from occurring and causing any damage to the materials, thus allowing them to remain viable for medical use later on. The two main advantages of tissue cryoprotection are storing and transporting the frozen material to when and where it is needed. One problem involved in cryoprotection is that the material to be frozen can con -
tain a considerable amount of water, which can create ice crystals when frozen caus -
ing lethal damage to the tissue. Because unprotected freezing of tissue is lethal, cryopreservants are used 
at very low temperatures to preserve structurally intact living cells and tissues. Cryoprotectants can reduce the amount of ice formed at any given temperature, but to be biologically acceptable, they must be able to penetrate into the cells and have low toxicity. Many compounds have such properties, including DMSO, glycerol, eth -
anediol, propylene glycol, and formamide, but often require high concentrations of the cryoprotective agent. DMSO is often the preferred cryoprotectant because it has been shown to cause the least harm to the tissue being frozen. 35
DMSO is a commonly used cryoprotectant also due to its high water solubility, 
rapid penetrability, and diminished osmotic damage at high concentrations normally used in cryopreservation protocols. 35
Preservation of cells and tissues at low temperatures requires the presence of 
a cryoprotectant that displays these qualities and display a low toxicity to the cell plasma membrane. DMSO possesses all three qualities. 36 The unusual ability of 
DMSO to dramatically depress the freezing point of water while maintaining viabil -
ity with many cell and tissue types has led to the use of this agent in cryopreserva -
tion media for stem cells derived from human umbilical cord blood and reproductive tissue. The role of hematopoietic stem cell transplants in the treatment of hematologic 
and nonhematologic malignancies is now widely used clinically. Hemopoietic  stem 
cell preservation and transplantation is an important part of the treatment of cancer patients who have undergone high-dose chemotherapy and irradiation for cancers 
such as lymphoma and leukemia. DMSO is a common cryopreservative for these 
cells, which are derived from bone marrow, peripheral circulatory system, or umbili -
cal cord blood. 37 DMSO is chosen as the standard cryoprotectant because it best 
prevents freezing damage to living cells.10 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
Many reports have appeared in the literature concerning adverse reactions in 
DMSO-preserved stem cells following transplantation in recipients. These reactions 
include nausea, vomiting, abdominal cramps, chills, cardiac arrhythmias, neurologi -
cal symptoms, and respiratory arrest.38,39 These adverse reactions by stem cell trans -
plants preserved in DMSO may be caused by the amount of infusate used, amount of cells being infused, and the rate of infusion. 36
These adverse reactions are transient for the most part and can be minimized 
when the infusate is optimized to the medical condition of the individual patient.40 
Also, when DMSO is used with normal saline and albumin at a concentration of 10%, the incidence of these toxic reactions is diminished. 39 Severe adverse reactions 
after stem cell transplants are infrequent although, when they occur, patients may require clinical treatment. One trick that has shown antiemetic properties following stem cell transplants using DMSO as cryoprotectant is the use of orange-flavored ice lollies. The relief of nausea and vomiting may be due to the vasoconstrictive action of ice on the stomach and the masking of DMSO’s garlic odor by the orange flavor of the ice. 41
A robust and slow-freezing cocktail containing DMSO and hydroxyethyl starch 
in saline was recently developed to freeze human pluripotent stem cells with a high recovery rate (80%) of the cells after thawing. 42 The method has not been tested 
clinically on patients yet but promises to provide storage of human pluripotent stem cells easily, effectively, and economically in the future. The potential of gonadal cryobiology in the conservation of fertility is now fully 
realized. Freezing semen to safeguard male fertility is an option available to men undergoing sterilizing chemotherapy. DMSO is the cryoprotectant most commonly used in many hospitals as a stan -
dard procedure for autologous peripheral blood progenitor cell transplantation for the treatment of chemosensitive malignancies. DMSO IN THE SEA AND THE ATMOSPHERE
A salty sea smell can usually be felt when one is near the ocean but the smell is not from the salt alone. The smell comes from wind-driven white caps and breaking waves, which is composed not only of salt but also of gases that diffuse across the air–sea interface, many of which are synthesized and emitted by microalgae and degraded by bacteria and phytoplankton. 43 One of these gases found to occur in 
ocean surface waters is dimethyl sulfide, a DMSO metabolite with a sulfur-based compound that has a strong characteristic odor. While dimethyl sulfide may sound like a noxious pollutant, it is a naturally produced biogenic gas essential for the earth’s biogeochemical cycles. Sulfur is also an element of the earth and is essential to life. It is the eighth most 
prevalent element in the human body, not as sulfur itself but always in combination with other elements, most often, in complex molecules and, less often, in simple 
molecules such as DMSO. DMSO can be found in the atmosphere. 44 Water vapor is transferred to the atmo -
sphere as a gaseous dimethyl sulfide, which is then oxidized to tropospheric sulfate 
aerosols, and these particle aerosols condense on cloud particles, forming the water 11 Chemistry of DMSO
droplets that make up clouds.45 Clouds as well as marine life can affect the earth’s 
radiation balance and markedly influence its temperature and climate. Recent findings show that the amount of dimethyl sulfide entering the atmo -
sphere could decrease in the future due to atmospheric oxidation of this DMSO 
metabolite by greenhouse gases.46,47 Such oxidation of dimethyl sulfide can lead 
to climate changes by increasing cloud albedo, a condition where clouds reflect more solar radiation contributing to the greenhouse effect. The greenhouse effect is a process by which thermal radiation from the planet’s surface is absorbed by greenhouse gases, such as CO
2 in the atmosphere, and reradiated in all directions, 
including back to the earth’s surface where the average temperature is increased.47 
As  CO2 levels rise in the atmosphere due to human activities, the ocean pH is 
 acidified, an effect that leads to lower plankton production of dimethyl sulfide con -
centrations, with the consequence of less dimethyl sulfide in the atmosphere and more global warming. 48
Dimethyl sulfide makes up 95% of the natural marine flux of sulfur gases to the 
atmosphere, and scientists estimate that the flux of marine dimethyl sulfide supplies about 50% of the global biogenic source of sulfur to the atmosphere. 46 Dimethyl 
sulfide is oxidized in the marine atmosphere to other sulfur-containing compounds, such as DMSO and its second metabolite dimethyl sulfone, as well as sulfur dioxide, methanesulfonic acid, and sulfuric acid. 49
There is evidence that DMSO and its second metabolite dimethyl sulfone may 
be as significantly present as dimethyl sulfide in marine rain and marine air masses. Measures in central equatorial Pacific rain were reported to contain 1–10 µg/L of 
both DMSO and dimethyl sulfone, which are near the concentrations found for dimethyl sulfide in marine sulfur transport. 48,49 This observation suggests that a par -
tially reversible loop in the sulfur transport cycle of marine rain and air gases may be operating between DMSO and its metabolites and could play a critical role in climate, temperature, and marine life. REFERENCES
 1. Saytzef f A. Ueber die Einwirkung von Saltpetersäure auf Schwefelmethyl und 
Schwefeläthyl (On the effect of nitric acid on methyl sulfide and ethyl sulfide). Ann 
Chem Pharm . 1867;144:148–156. 2. MacGre gor WS. The chemical and physical properties of DMSO. Ann NY Acad Sci . 1967;141(1):3–12. 3. Steck er PG. (ed.). Lignin , V ol. 8. Merck Index, Rahway, NJ, 1968; p. 619. 4. Epstein WW, Sweat FW. Dimethyl sulfoxide oxidations. Chem Rev. 1967;67:247–260. 5. Y u ZW, Quinn PJ. Dimethyl sulphoxide: A review of its applications in cell biology. Biosci Rep . 1994;14(6):259–281. 6. Szmant HH. Chemistry of DMSO. In Dimethyl Sulfoxide, Basic Concepts , eds. S.W. Jacob, E.E. Rosenbaum, D.C. Wood. Marcel Dekker, Inc., New York, 1971; 
pp. 1–94. 7. Da vid NA. The pharmacology of dimethyl sulfoxide. Annu Rev Pharmacol . 1972;12:353–374. 8. Römpp Chemie-Lexikon , Bde, Thieme, Stuttgard, 2006; p. 114. 9. Martin D, Hauthal G. Dimethyl Sulfoxide  (Trans by Halberstadt ES). Van Nostrand 
Reinhold, Akademie-Verlag, Berlin, 1971.12 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
 10. Kharasch N, Thyagarajan BS. Structural basis for biological activities of dimethyl sulf -
oxide. Ann NY Acad Sci . 1983;411:391–402. 11. Szmant HH. Ph ysical properties of dimethyl sulfoxide and its function in biological 
systems. Ann NY Acad Sci . 1975;243:20–23. 12. W indholz M. (ed.). The Merck Index , 10th edn. Merck, Rahway, NJ, 1983. 13. Przestalski S, Sarapuk J, Kleszczy ńska H, Gabrielska J, Hladyszowski J, Trela Z, 
Kuczera J. Influence of amphiphilic compounds on membranes. Acta Biochim Pol . 2000;47(3):627–638. 14. Jacob SW , Rosenbaum EE, Wood DC. Dimethyl Sulfoxide , V ol. 1. Marcel Dekker, 
New York, 1971. 15. T angerman, A. Measurement and biological significance of the volatile sulfur com -
pounds hydrogen sulfide, methanethiol and dimethyl sulfide in various biological matri -
ces. J Chromatogr B. 2009;877(28):3366–3377. 16. Jacob SW, Bischel M, Herschler RJ. Dimethyl sulfoxide (DMSO): A new concept in 
pharmacotherapy. Curr Ther Res Clin Exp . 1964;6:134–135. 17. W illiams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev . 2004;56(5):603–618. 18. Jacob SW , Wood DC. Dimethyl sulfoxide (DMSO). Toxicology, pharmacology, and 
clinical experience. Am J Surg . 1967;114(3):414–426. 19. W elch WJ, Brown CR. Influence of molecular and chemical chaperones on protein fold -
ing. Cell Stress Chaperones . June 1996;1(2):109–115 (Review: Erratum in: Cell Stress 
Chaperones . September 1996;1(3):207.) 20. Robben JH, Sze M, Knoers NV , Deen PM. Rescue of vasopressin V2 receptor 
mutants by chemical chaperones: Specificity and mechanism. Mol Biol Cell . January 
2006;17(1):379–386. 21. Bur g MB, Ferraris JD. Intracellular organic osmolytes: Function and regulation. J Biol 
Chem. 2008;283(12):7309–7313. 22. Street TO, Bolen DW, Rose GD. A molecular mechanism for osmolyte-induced protein 
stability. Proc Natl Acad Sci USA . 2006;103(38):13997–14002. 23. P app E, Csermely P. Chemical chaperones: Mechanisms of action and potential use. Handb Exp Pharmacol . 2006;172:405–416. 24. Mackay GA, Knight RSG, Ironside JW . The molecular epidemiology of variant CJD. Int J Mol Epidemiol Genet . 2011;2(3):217–227. 25. Aguzzi A. Unraveling prion strains with cell biology and organic chemistry. Proc Natl 
Acad Sci . 2008;105(1):11–12. 26.
Dimethyl_Sulfoxide_(DMSO)_in_Trauma_and_Disease_[2015].txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        ISBN: 978-1-4987-1467-9
9 781498 71467990000K25303
Dimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
STANLEY W. JACOB
JACK C. DE LA TORRE
JACOB • DE LA TORRE
CHEMISTRY
First isolated as a chemical compound by a Russian chemist in 1866,  
dimethyl sulfoxide (DMSO) proved to be a near-perfect solvent for  
decades before its remarkable biological and medical activities were  
discovered. DMSO is one of the most prodigious agents ever to come  
out of the world of drug development. Its wide range of biological actions 
involving plants, animals, and humans has led to the publication of tens  
of thousands of articles in the scientific literature. Dimethyl Sulfoxide (DMSO) in Trauma and Disease examines the major 
clinical uses of DMSO in humans as supported by basic evidence derived from experiments in animals, including its effects in disorders such as osteoarthritis, interstitial cystitis, gastrointestinal inflammatory changes, scleroderma, respiratory distress, myasthenia gravis, cardiac disease, traumatic brain injury, and Alzheimer’s disease. The effects of DMSO on pain, cancer, stroke, and spinal cord injury are 
also discussed. The book explores how its chemical structure is able  
to react and deactivate toxic molecules generated by DNA damage, free radical formation, inflammation, oxidation, and infection. For the first time, the collective data on the biological, chemical, and medical actions of DMSO are presented and analyzed from the published scientific literature. Clearly written, the book incorporates easy-to-understand scientific  
descriptions that appeal both to health care professionals and the  
millions of people worldwide who have used DMSO for an assortment of 
ailments as a prescriptive or off-label medication. Dimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
K25303_Cover_PubGr. indd   All Pages 2/11/15   2:38 PMDimethyl Sulfoxide  
(DMSO) in Trauma  
and DiseaseDimethyl Sulfoxide  
(DMSO) in Trauma  
and Disease
STANLEY W.
A Russian chemist, Alexander Saytzeff, in 1866.
Who is credited with the first isolation of dimethyl sulfoxide (DMSO) as a chemical compound?
The book examines the major clinical uses of DMSO in humans, supported by evidence from animal experiments, including its effects in disorders such as osteoarthritis, interstitial cystitis, gastrointestinal inflammatory changes, and more.
What is the purpose of the book "Dimethyl Sulfoxide (DMSO) in Trauma and Disease"?
The primary barrier is the stratum corneum, and DMSO enhances permeability by fluidizing lipids and reducing the amount of ice crystals formed during freezing.
What is the primary barrier to molecules penetrating the skin, and how does DMSO overcome this barrier?
DMSO is being researched as an electrolyte for rechargeable Li+–O2 batteries due to its high polarity and ability to dissolve a wide range of solutes.
What is the purpose of DMSO as an electrolyte in rechargeable batteries?
DMSO is preferred due to its ability to penetrate rapidly and cause minimal damage to the tissue being frozen.
What is the main advantage of using DMSO as a cryoprotectant?