Effect Of Dimethyl Sulphoxide Research Articles

The Safety Factor for Neuromuscular Transmission: Effects of Dimethylsulphoxide, Cannabinoids and Synaptic Homeostasis.

BackgroundIn myasthenia gravis, impaired postsynaptic sensitivity to acetylcholine results in failure of neuromuscular transmission and fatiguing muscle weakness.ObjectiveDevelop an ex vivo muscle contraction assay to test cannabinoids and other substances that might act on the myasthenic neuromuscular junction to restore control of the muscle.MethodsTubocurarine was added to an ex vivo, mouse phrenic nerve-hemidiaphragm muscle preparation to reduce acetylcholine sensitivity. This produced a myasthenia-like decrement in twitch force during a train of 10 nerve impulses (3 / sec). Endplate potential (EPP) recordings were used to confirm and extend the findings.ResultsSurprisingly, addition to the bath of dimethylsulphoxide (DMSO), at concentrations as low as 0.1%(v/v), partially reversed the decrement in nerve-evoked force. Intracellular electrophysiology, conducted in the presence of tubocurarine, showed that DMSO increased the amplitudes of both the spontaneous miniature EPP (MEPP) and the (nerve-evoked) EPP. In the absence of tubocurarine (synaptic potentials at physiological levels), an adaptive fall in quantal content negated the DMSO-induced rise in EPP amplitude. The effects of cannabinoid receptor agonists (solubilized with DMSO) in the contraction assay do not support their further exploration as useful therapeutic agents for myasthenia gravis. CP 55,940 (a dual agonist for cannabinoid receptor types 1 and 2) reversed the beneficial effects of DMSO.Conclusions:We demonstrate a powerful effect of DMSO upon quantal amplitude that might mislead pharmacological studies of synaptic function wherever DMSO is used as a drug vehicle. Our results also show that compounds targeting impaired neuromuscular transmission should be tested under myasthenic-like conditions, so as to avoid confounding effects of synaptic homeostasis.

Dimethyl sulphoxide and dimethyl sulphone are potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2

Aims Reactive oxygen species (ROS) are highly diffusable and reactive molecules which modulate gene transcription, particularly of pro-inflammatory cytokines which play a crucial role in the nascency and progression of chronic inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). Since thiols could be potent inhibitors of the production of cytokines, the effects of dimethyl sulphoxide (DMSO) and dimethyl sulphone (DMS) on constitutive and IL-1β-induced IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2 were evaluated. Main methods C-28/I2 cells were incubated for 12 h with different concentrations of DMSO or DMS. The secretion of IL-6 and IL-8 was quantified by enzyme-linked immunosorbent assays (ELISAs). The impact of DMSO and DMS on the regulation of p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) was confirmed by Western blot experiments. Furthermore, C-28/I2 cells were stimulated with IL-1β in the absence or presence of DMSO and DMS and IL-6 and IL-8 expression was quantified by ELISAs and quantitative real-time polymerase chain reaction (qRT-PCR). Key findings C-28/I2 cells constitutively expressed large quantities of IL-6 and IL-8. Long-term exposure of cells to DMSO (1%) or DMS (100 mM) led to a dramatic downregulation of IL-6 and IL-8 expression which was accompanied by the deactivation of ERK1/2. Both substances also blocked IL-1β-induced IL-6 and IL-8 expression. Significance In this study, we demonstrate that both DMSO and DMS represent strong anti-inflammatory properties by blocking constitutive as well as IL-1β-induced IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2.

Effects of dimethyl sulphoxide (DMSO) on aggregation of human blood platelets.

The effects were examined of the universal solvent dimethyl sulphoxide (DMSO) on human platelet aggregatory activity, in-vitro, of the endogenous mediators ADP, adrenaline, arachidonic acid, collagen and PAF-acether which are believed to play important roles in cardiovascular diseases in man. DMSO inhibited aggregation induced by all of the mediators in the order ADP greater than adrenaline = arachidonic acid = PAF-acether greater than collagen. Since DMSO is widely used as a solvent for drug substances, an awareness of its intrinsic activity in any such evaluations is essential.

Effects of Dimethyl Sulphoxide and Dexamethasone on mRNA Expression of Myogenesis- and Muscle Proteolytic System-related Genes in Mouse Myoblastic C2C12 Cells

We examined the time course of mRNA expression of myogenic cell differentiation- and muscle proteolytic system-related genes in cultures of C2C12 cells during differentiation from myoblasts to myotubes. Furthermore, we treated C2C12 myotubes with dimethyl sulphoxide (DMSO) and dexamethasone (Dex), and examined changes in these mRNA levels. Myogenin (Myog), Atrogin1, forkhead box O1 (Foxo1) and Capn1 mRNA levels increased in C2C12 cells differentiating from myoblasts to myotubes, whereas Myf5 mRNA levels decreased. Although genes such as MRF4, Foxo3a, UbB, Capn1 and MuRF1 mRNAs in the myotubes were affected by DMSO exposure, mRNA levels of other genes were not markedly affected by exposure to 0.02% or 0.5% DMSO. Myf5, MRF4, Atrogin1, Foxo3 and MuRF1 mRNA levels were elevated by Dex at all time points, Cbl and Capn1 mRNA levels were significantly elevated by Dex at 8 h, and Myog mRNA levels were significantly elevated by Dex at 24 h. However, CtsH mRNA levels decreased significantly with Dex at 24 h. This study provides a useful database of gene profiles that are differentially expressed throughout myogenic cell differentiation and the muscle proteolytic system.

Effect of dimethyl sulphoxide on oxidative stress, activation of mitogen activated protein kinase and necrosis caused by thioacetamide in the rat liver

Thioacetamide (400 mg/kg body weight, i.p.) was administered to rats. After 12 h the activity of plasma glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) was significantly higher than that of the control group, and after 24 h plasma GOT and GPT activities strongly increased. These results indicated that the necrotic process was initiated at about 12 h and developed thereafter. By co-administration of dimethyl sulphoxide (DMSO, 18 and 1 h before, and 8 h after administration of thioacetamide: each time, 2.5 ml/kg body weight, p.o.), plasma GOT and GPT were significantly decreased and were even comparable to the control group, showing that DMSO totally prevented the necrotic action of thioacetamide. After 12 and 24 h of thioacetamide administration, the hepatic level of vitamin C, the most sensitive chemical indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 12 h after thioacetamide intoxication and thereafter. DMSO totally restored the liver vitamin C level, demonstrating that DMSO effectively ameliorated the oxidative stress caused by thioacetamide, resulting in the prevention of necrosis of the liver. Phosphorylated c-Jun NH2-terminal kinase (JNK) significantly increased transiently 12 h after treatment with thioacetamide. These results indicated that oxidative stress and the activation of JNK took place almost simultaneously. Phosphorylated extracellular signal-related kinase (ERK) 2 was significantly increased 6–12 h after thioacetamide injection. Phosphorylated p38 MAPK (mitogen activated protein kinase) was significantly decreased 24 h after administration of thioacetamide. DMSO treatment inhibited the change of these MAPKs by thioacetamide, corresponding with the prevention of the liver necrosis as well as the attenuation of oxidative stress.

Effect of dimethyl sulphoxide on oxidative stress, activation of mitogen activated protein kinase and necrosis caused by thioacetamide in the rat liver

Effect of dimethyl sulphoxide on oxidative stress, activation of mitogen activated protein kinase and necrosis caused by thioacetamide in the rat liver

Inhibition of methylcholanthrene-induced skin carcinogenesis in hairless mice by the membranelabilizing agent DMSO

The effects of dimethyl sulphoxide (DMSO) are in some respects similar to those of retinoids. DMSO has the ability to penetrate cellular membranes and to enhance the penetration of other molecules. It may be reasonable to assume that DMSO treatment results in differentiation of cells, possibly through membrane-mediated events. This may be of importance for the study of the carcinogenic process. The release of a certain amount of lysosomal enzymes to the extracellular space is a normal function of the cell (Hickman & Neufeld, 1972), and a certain release of the cytoplasmic and lysosomal enzymes to the extracellular space is not necessarily deleterious for the cells (Volden, Haugen & Skrede, 1980). The purpose of the present investigation was to study the possible effects of DMSO on methylcholanthrene-induced skin carcinogenesis. Since the uptake of lysosomal enzymes by cultured cells appears to involve a membrane receptor process, the effects of the carcinogen and the solvents on the rate of secretion of lysosomal enzymes and lactate dehydrogenase from HeLa cells were investigated.

1H chemical shifts in NMR: Part 23, the effect of dimethyl sulphoxide versus chloroform solvent on 1H chemical shifts

The 1H chemical shifts of 124 compounds containing a variety of functional groups have been recorded in CDCl3 and DMSO-d6 (henceforth DMSO) solvents. The 1H solvent shift Delta delta = delta(DMSO) - delta(CDCl3) varies from -0.3 to +4.6 ppm. This solvent shift can be accurately predicted (rms error 0.05 ppm) using the charge model of alpha, beta, gamma and long-range contributions. The labile protons of alcohols, acids, amines and amides give both, the largest solvent shifts and the largest errors. The contributions for the various groups are tabulated and it is shown that for H.C.C.X gamma-effects (X = OH, NH, =O, NH.CO) there is a dihedral angle dependence of the gamma-effect. The group contributions are discussed in terms of the possible solvent-solute interactions. For protic hydrogens, hydrogen bonding is the dominant interaction, but for the remaining protons solvent anisotropy and electric field effects appear to be the major factors.

Effects of dimethylsulphoxide on mice arsenite-induced dysmorphogenesis in embryo culture and cytotoxicity in embryo cells

Dimethylsulphoxide (DMSO) is a widely used vehicle for water insoluble compounds in experimental studies. Nevertheless, little is known about its potential impact on dysmorphogenesis caused by reactive oxygen species (ROS). In order to evaluate if DMSO at concentrations used as vehicle can alter in vitro sodium arsenite (Asi) teratogenicity and cytotoxicity, mouse embryos with 4–5 somites were grown for 48 h in Asi 0.4 and 4 μM, with and without 0.1% DMSO (v/v). Also embryonic mesenchymal cell were cultured, using mesenchymal mouse embryo cells obtained from gestation day 11 and treated with DMSO 0.1%, 0.2% and 0.5% (v/v) 15 min before Asi was added at final concentrations of 0.4 and 4 μM. Cytotoxicity and intracellular ROS production, were evaluated with MTT and 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H 2DCFDA), respectively. Results indicated that Asi produced growth retardation and abnormal development. Main malformations involved neural tube closure defects, abnormal rotation and optic vesicle defects among others. Co-treatment with DMSO partially reduced neural tube defects as well as facial dysmophology. Asi reduced cell viability inversely to the level of ROS production, and DMSO returned cellular viability to control values by reducing ROS intracellular production. In summary, the protective effect observed for DMSO appeared to reflect free radical scavenger properties, though other mechanisms independent to ROS production may have also been involved.

Effect of dimethyl sulphoxide on the crystal structure of porcine pepsin

The structure of porcine pepsin crystallized in the presence of dimethyl sulphoxide has been analysed by X-ray crystallography to obtain insights into the structural events that occur at the onset of chemical denaturation of proteins. The results show that one dimethyl sulphoxide molecule occupies a site on the surface of pepsin interacting with two of its residues. An increase in the average temperature factor of pepsin in the presence of dimethyl sulphoxide has been observed indicating protein destabilization induced by the denaturant. Significant increase in the temperature factor and weakening of the electron density have been observed for the catalytic water molecule located between the active aspartates. The conformation of pepsin remains unchanged in the crystal structure. However, the enzyme assay and circular dichroism studies indicate that dimethyl sulphoxide causes a slight change in the secondary structure and complete loss of activity of pepsin in solution.

Effects of Dimethyl Sulphoxide Against Liver Injury Caused by Carbon Tetrachloride in Rats

A single oral dose of 1.25 ml kg−1 of carbon tetrachloride (CCl4) was sufficient to induce significantly elevated levels of serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) together with signs of acute centrilobular necrosis and fatty accumulation in liver tissue. Dimethyl sulfoxide (DMSO) in different dosages (2750 mg kg−1, 5500 mg kg−1 and 8250 mg kg−1; dissolved in saline) were screened for their potential activity against CCl4-induced liver injury in Sprague-Dawley rats. The results showed that post-administration of high dosages (5500 mg kg−1 and 8250 mg kg−1) of DMSO-saline solution significantly reduced CCl4-induced acute elevation in the levels of SGPT and SGOT. The same result was observed in histopathological study of liver tissue. DMSO, in high doses, probably prevented CCl4-induced liver injury through its antioxidant, anti-inflammatory or microsomal enzyme arresting properties.

Effects of dimethyl sulphoxide and heparin on stretch‐activated ATP release by bladder urothelial cells from patients with interstitial cystitis

To determine whether dimethyl sulphoxide (DMSO) and heparin reduce the greater stretch-activated ATP release in interstitial cystitis (IC), as ATP serves as a nocio-neurotransmitter in the bladder, and thus explain their beneficial effects in patients with IC (a disease characterized by hypersensory bladder symptoms). Bladder epithelia in IC release more ATP in response to stretch than do control samples. Both DMSO and heparin are used intravesically to treat IC; such agents can modulate urothelial function because they directly contact bladder urothelium. Biopsies taken from patients with IC and from control subjects were grown in primary cultures using established cell-culture techniques. Cultured urothelial cells were stretched with the Flexcell device (Flexcell International Corp., McKeesport, PA, USA) and supernatant ATP was measured, using a luciferin-luciferase assay. DMSO (0.1%, 0.5% and 1%) or heparin (50, 200, 800 and 1600 U) was added to the cells at the start of the stretch experiments and the ATP released into the supernatant measured. Cell viability was also determined using Trypan Blue staining. IC cells released significantly more ATP in response to stretch than did control cells. This increased release of ATP by stretched IC cells was significantly blocked by adding DMSO or heparin at all concentrations used. Heparin appeared to have a greater dose-dependent effect on ATP release than did DMSO. These findings are consistent with the hypothesis that the urothelium provides sensory input via ATP release and that this process is increased in IC. Furthermore, stretch-activated ATP release was blocked by adding DMSO and heparin, both intravesical agents commonly used to treat the symptoms of IC. This study supports the notion that purinergic-targeted therapy is warranted in treating IC. Further studies are needed to determine the mechanisms of increased ATP release by IC urothelial cells.

The effect of dimethylsulphoxide (DMSO) on the membrane conductivity of an isolated vacuole.

The effect of dimethylsulphoxide (DMSO) on the membrane conductivity of an isolated vacuole.

The effect of dimethyl sulphoxide on the structure and phase behaviour of palmitoleoylphosphatidylethanolamine

The thermotropic phase behaviour and structure of a nonbilayer-forming lipid, 1-palmitoyl-2-oleoyl-phosphatidylethanolamine, dispersed in water and in aqueous solutions of up to 50 wt% dimethyl sulphoxide (DMSO) have been characterised using synchrotron X-ray diffraction methods. It was found that the presence of DMSO in the solvent induced an increase in the temperature of lamellar-gel to lamellar-liquid-crystal phase transition and a decrease in the temperature of the lamellar-liquid-crystal to inverted-hexagonal phase transition of the phospholipid. The presence of DMSO also caused a decrease in the X-ray repeat spacings of all the phases studied. Electron density profiles of the phospholipid dispersed in water and 50 wt% DMSO in the bilayer gel state were calculated. The presence of 50 wt% DMSO caused the apparent disappearance of the solvent layer separating phospholipid bilayers in the gel state. The results suggest that DMSO contributes to the bilayer electron density profile and that the amphiphilic solvent molecules partition into the interfacial region.

The effect of dimethyl sulphoxide on the induction and repair of double-strand breaks in human cells after irradiation with gamma-rays and accelerated ions: rapid or slow repair may depend on accessibility of breaks in chromatin of different compactness

Purpose : The repair of double-strand breaks (dsb) in mammalian cells is characterized by a rapid phase with a half-life of less than half an hour and a slower phase that lasts for many hours. The proportion of slow repair increase with LET and it has been suggested that the slow repair component consists of more complex damage and is more deleterious to the cells. To see if removal of OH radicals could remove part of the damage in complex dsb and make them easier to repair, human cells were irradiated in the presence of dimethyl sulphoxide (DMSO). Methods : Induction and repair of dsb were studied by neutral elution in human VH10 cells exposed to gamma-rays, helium ions (mean LET 40 keV/mum) and 80 and 125 keV/mum monoenergetic nitrogen ions in the presence and absence of 2M DMSO. Results : Incubation of cells exposed to gamma-rays, 40 keV/mum helium and 80 keV/mum N ions demonstrated that scavenging of OH radicals by DMSO removed most of the rapid repair component. The response to DMSO was less marked after 125 keV/mum nitrogen ions, where about half of the rapid repair was resistant to DMSO. Conclusions : It is unlikely that the complexity of dsb is responsible for the slow repair because the removal of OH radicals did not make the breaks easier to repair. Instead, it is suggested that rapid and slow repair can be explained on the basis of how different parts of the chromatin are accessible to repair enzymes.

Effect of Dimethyl Sulphoxide On Necrosis of Skin Flaps in Rats

I da Silva Duarte, HF de Carvalho Gomes, LM Ferreira. Effect of dimethyl sulphoxide on necrosis of skin flaps in rats. Can J Plast Surg 1998;6(2):93-97. The effect of dimethyl sulphoxide (DMSO) on necrosis of the distal portion of random skin flaps was studied. Twenty-eight Wistar-EPM rats each had a random skin flap created that measured 10×4 cm. A plastic barrier was interposed between the flap and the bed. Rats in group 1 received distilled water and those in group 2 received DMSO 2 mL/kg/day by intragastric lavage for seven days. The percentages of necrotic area were calculated in the two groups, and malondialdehyde (MDA) was measured in the serum, in the samples of normal skin and in the transition region from viable to necrotic skin. Statistical analysis showed that DMSO was efficient in reducing the necrotic areas and MDA values compared with results from group 1. Statistical analysis also revealed that the action of DMSO as an antioxidant can be inferred to be the mechanism responsible for the results obtained.

Effect of dimethylsulphoxide (DMSO) with methyltert-butyl ether (MTBE) and ethyl propionate (EP) in dissolving capacity of cholesterol gallstone in vitro

Effect of dimethylsulphoxide (DMSO) with methyltert-butyl ether (MTBE) and ethyl propionate (EP) in dissolving capacity of cholesterol gallstone in vitro

Inhibitors of Glutathione Reductase as Potential Antimalarial Drugs Kinetic Cooperativity and Effect of Dimethyl Sulphoxide on Inhibition Kinetics

We have developed inhibitors of glutathione reductase that improve on the inhibition of literature lead compounds by up to three orders of magnitude. Thus, analogues of Safranine O and menadione were found to be strong, reversible inhibitors of yeast glutathione reductase. Safranine O exhibited partial, uncompetitive inhibition with Ki and alpha values of 0.5 mM and 0.15, respectively. Thionine O was a partial (hyperbolic) uncompetitive inhibitor with Ki and alpha values of 0.4 microM and 0.15, respectively. LY83583 and 2-anilino-1,4-naphthoquinone also showed (hyperbolic) partial, uncompetitive inhibition with micromolar Ki values. For Nile Blue A a model for two-site binding with (parabolic) uncompetitive inhibition fitted the data with a Ki value of 11 microM and a kinetic cooperativity between the sites of 0.12, increased to 0.46 by preincubation of the enzyme and Nile Blue A in the presence of glutathione disulphide. Analysis of the effects of preincubation on the kinetics and cooperativity indicated the possibility of a slow conformational change in the homodimeric enzyme, the first such indication of kinetic cooperativity in the native enzyme to our knowledge. Further evidence of conformational changes for this enzyme came from studies of the effects of dimethyl sulphoxide which indicated that this co-solvent, which at low concentrations has no apparent effect on initial velocities under normal assay conditions, induced a slow conformational change in the enzyme. Thionine O, Nile Blue A and LY83583 were redox-cycling substrates producing superoxide ion, detectable by means of cytochrome c reduction, but leading to no loss of glutathione reductase activity, under aerobic or anaerobic conditions. The water-soluble Safranine analogues Methylene Blue, Methylene Green, Nile Blue A and Thionine O (5 mg/kg i.p. x 5) were effective antimalarial agents in vivo against P. berghei, but their effect was small and a higher dose (50 mg/kg i.p. x 1) was toxic in mice. Comparison was made with human glutathione reductase and its literature-reported interactions with several tricyclic inhibitors as studied by X-ray diffraction. It is possible that the conformational changes detected in the present study from alterations in detailed kinetic inhibition mechanisms may shed light on information transfer through the glutathione reductase molecule from the dimer interface ligand pocket to the active-site.

The modulation of membrane structure and stability by dimethyl sulphoxide (review).

Dimethyl sulphoxide is a widely used agent in cell biology. It is well known as a cryoprotectant, cell fusogen and a permeability enhancing agent. These applications depend, to a greater or lesser extent, on the effect of dimethyl sulphoxide on the stability and dynamics of biomembranes. The aim of this review is to examine progress of the research which has been directed towards studies of the interactions between dimethyl sulphoxide and membranes, particularly that with the lipid components of cell membranes, as seen in its effects on model membrane systems. Models are proposed to explain the mechanism whereby dimethyl sulphoxide may mediate its effects on biological functions by its effects on the stability and properties of the membrane lipid matrix.

Effect of dimethyl sulphoxide on necrosis of skin flaps in rats

Effect of dimethyl sulphoxide on necrosis of skin flaps in rats