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Elucidation of dimethylsulfone metabolism in rat using a 35S radioisotope tracer method
Abstract
The metabolism of dimethylsulfone was quantified for possible medical applications based on the hypothesis that the agent may be metabolized to yield methionine or its metabolites. The 35S-labeled dimethylsulfone and methionine are orally administrated to rat. Over 80% of the administrated dimethylsulfone is metabolized in the rats tissues, and 59.7–79.1% of it is then excreted into the urine as 35S-containing metabolites; 3.5–10.3% of the same remains incorporated in the tissues. The uptake of radioactivity, though different from the quantity of methionine in percentage at the retained site, is observed in the blood, spleen and hair, and over 80% of the administered [35S] dimethylsulfone is excreted the same day. Meanwhile, the distribution of the 35S concentrations of both agents in the rat system suggests that this compound had been metabolized to yield certain sulfur-containing compounds.
... Pharmacokinetic studies indicate that MSM is rapidly absorbed in rats [63,64] and humans [65], taking 2.1 h and <1 h, respectively. Similar studies utilizing DMSO in monkeys demonstrate rapid conversion of DMSO to MSM within 1-2 h after delivery via oral gavage [66]. ...
... In rats, between 59% and 79% of MSM is excreted the same day as administration in urine, either unchanged or as another S-containing metabolite [64]. Urine is the most common form of excretion as MSM has been detected in urine of rats [63,67], rabbits [4,5], bobcats [68], cheetahs [69], dogs [70], monkeys [66], and humans [4,62,71,72]. ...
... Urine is the most common form of excretion as MSM has been detected in urine of rats [63,67], rabbits [4,5], bobcats [68], cheetahs [69], dogs [70], monkeys [66], and humans [4,62,71,72]. Additionally, excretion of MSM can be contained in feces [63,64] or several other biofluids including cow's milk [54,73], red deer tail gland secretion [74], and human saliva [75]. ...
Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.
... Otsuki et al. (17) investigated the distribution of oral MSM using a 35 S radioisotope tracer method in rats of different ages fed standardized diets. [ 35 S]MSM was administered daily for 7 days by gavage at a dose level of 470 mg/kg/day. ...
... There are many opportunities for sulfur to incorporate into biological molecules, especially when the animal feed has low sulfur content. Studies have demonstrated that sulfur from MSM can be incorporated into tissue proteins (9,17). ...
... Similar to the present study, Otsuki et al. (17) also reported an almost even tissue distribution of radioactivity following the administration of [ 35 S]MSM. Relatively high levels of 35 S were noted in blood, spleen, and hair tissues, compared to other tissues. ...
Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains, and beverages. More recently, it has been marketed as a dietary supplement worldwide. The objective of this study was to evaluate the pharmacokinetic profile and distribution of radiolabeled MSM in rats. Male Sprague-Dawley rats were administered a single oral dose of [35S]MSM (500 mg/kg), and blood levels of radioactivity were determined at different time points for up to 48 h. Tissue levels of radioactivity at 48 and 120 h and urine and fecal radioactivity levels were measured at different time points for up to 120 h following [35S]MSM administration to rats. Oral [35S]MSM was rapidly and efficiently absorbed with a mean tmax of 2.1 h, Cmax of 622 microg equiv/mL, and AUC0-inf of 15124 h.microg equiv/mL. The t1/2 was 12.2 h. Soft tissue distribution of radioactivity indicated a fairly homogeneous distribution throughout the body with relatively lower concentrations in skin and bone. Approximately 85.8% of the dose was recovered in the urine after 120 h, whereas only 3% was found in the feces. No quantifiable levels of radioactivity were found in any tissues after 120 h, indicating complete elimination of [35S]MSM. The results of this study suggest that [35S]MSM is rapidly absorbed, well distributed, and completely excreted from the body.
... Once absorbed, dietary MSM may be metabolized to produce metabolites with potential medical value, such as sulfur-containing amino acids [52]. MSM has an enhanced ability to penetrate cell membranes inside the body and cross the blood-brain barrier [38,53]. ...
... Earlier studies in rodents demonstrated that sulfur from MSM could be incorporated into tissue proteins [55]. Additionally, most MSM metabolites are excreted via the urine [52]. Thus, dietary MSM is required to maintain constant biological levels for beneficial effects due to its rapid metabolism and excretion [54]. ...
Oxidative stress is defined as an imbalance between pro-oxidants and anti-oxidants within biological systems, leading to tissue damage and compromising the health of afflicted animals. The incorporation of dietary anti-oxidants into chicken diets has been a common practice to improve the performance, health, and welfare of the host by protecting against oxidative stress-induced damage. Methyl sulfonyl methane (MSM), a naturally occurring organosulfur compound found in various plant sources, has demonstrated various beneficial biological properties, including anti-inflammatory and anti-oxidant properties in both in vitro and in vivo studies. MSM has been utilized as a dietary supplement for humans for its anti-oxidant, analgesic, and anti-inflammatory properties. It has also been administered to domestic animals, including cattle, pigs, and chickens, owing to its recognized anti-oxidant effect. This review summarizes the biological and physiological functions of dietary MSM in poultry.
... 17 Animal studies with radioactive dimethylsulfone have indicated that over 80% of orally administered dimethylsulfone is metabolized in rat tissues, while over 10% is incorporated into the body including hair. 18 The distribution of radioactive sulfur in the rat suggests that dimethylsulfone is metabolized to yield sulfur-containing compounds in the body. 18 MSM may donate sulfur to keratin, which could help strengthen the bonds between keratin molecules in the hair and nails. ...
... 18 The distribution of radioactive sulfur in the rat suggests that dimethylsulfone is metabolized to yield sulfur-containing compounds in the body. 18 MSM may donate sulfur to keratin, which could help strengthen the bonds between keratin molecules in the hair and nails. ...
... Upon entering the body, MSM exhibits fairly homogenous tissue distribution and even crosses the blood brain barrier where it is evenly distributed in white and gray matter of the brain [54][55][56][57][58] . In a study using MSM with radiolabeled sulfur, excretion of MSM is most often noted in urine unchanged or as another S-containing metabolite 59 . It was also detected in other excrements such as feces 59,60 or saliva 61 but in very minute quantities. ...
... In a study using MSM with radiolabeled sulfur, excretion of MSM is most often noted in urine unchanged or as another S-containing metabolite 59 . It was also detected in other excrements such as feces 59,60 or saliva 61 but in very minute quantities. Whole body biological half-life is suggested to be greater than 12 hours 52 . ...
... Early pharmacokinetic studies showed that *64% of [ 35 S]Me 2 SO 2 (21 mg/kg) was excreted within 24 h upon intraperitoneal administration to rats [236]. In a more recent study, the distribution of Me 2 SO 2 administered orally for 7 days using a 35 S radioisotope tracer found that [ 35 S] Me 2 SO 2 (470 mg/kg/day) was excreted in urine (*70%) and feces (*10%) [237]. The highest levels of radioactivity were found in hair, blood, and spleen [237]. ...
... In a more recent study, the distribution of Me 2 SO 2 administered orally for 7 days using a 35 S radioisotope tracer found that [ 35 S] Me 2 SO 2 (470 mg/kg/day) was excreted in urine (*70%) and feces (*10%) [237]. The highest levels of radioactivity were found in hair, blood, and spleen [237]. Further investigations of Me 2 SO 2 pharmacokinetics in rats was performed by Magnuson et al. [238]. ...
Inorganic selenium and oxo-sulfur compounds are widely available in dietary supplements and have been extensively studied for their antioxidant and anticancer properties. Although many in vivo and clinical trials have been conducted using these compounds, their biochemical and chemical mechanisms of efficacy are the focus of much current research. This review discusses the ability of inorganic selenium compounds, such as selenite, and selenate, to prevent damage from reactive oxygen species as well as their ability to promote cell death by reactive oxygen species generation. Oxo-sulfur and selenium compounds, such as allicin, dimethyl sulfone, methionine sulfoxide, and methylselenenic acid also have similar abilities to act as both antioxidants and pro-oxidants, but the mechanisms for these behaviors are distinctly different from those of the inorganic selenium compounds. The antioxidant and pro-oxidant properties of these small-molecule sulfur and selenium compounds are extremely complex and often greatly depend on experimental conditions, which may explain contradictory literature reports of their efficacy.
... However, there are no significant effects on the content of S on d 0 and d 65 in our study. A relatively high concentration of [ 35 S] MSM was detected in the blood, spleen, and hair tissues, and the administered MSM might have been metabolized to yield certain sulfur-containing compounds, such as keratin, a key component of hair and nail in rats (Otsuki et al., 2002). The study also discusses the relationships between the amounts of MSM and Met, and the results show that there is no clear evidence to support the hypothesis that MSM may be metabolized to generate methionine or its metabolites. ...
Methylsulfonylmethane (MSM) is a natural sulfur-containing organic substance that has many biological functions, such as antioxidant, anti-inflammatory, skin nourishing, and hair growth-promoting effects. This study was conducted to determine the effect of MSM supplementation on growth performance, antioxidant capacity, and hair quality in kittens. A total of 21 Ragdoll kittens were assigned to three diets by initial body weight and gender: basal diet supplemented with 0%, 0.2%, and 0.4% MSM (CON, LMSM, and HMSM groups) for 65 days. During the whole period, the food intake of kittens in the MSM-treated groups tended to be higher (P < 0.10) compared with the CON group, and the average daily gain (ADG) had no significant difference when compared to the kittens in the CON group (P > 0.05). Antioxidant capacity had no significant difference (P > 0.05) among the groups. The scale thickness of hair tended to be smaller in the LMSM group compared to the CON group (P < 0.10) and decreased significantly (P < 0.05) over time from d 0 to d 65 in the LMSM group, indicating the improvement of hair quality. Besides, supplementation with LMSM increased bacterial diversity. Kittens fed MSM had no significant differences in fecal genus at the end of the study. No significant differences in fecal short-chain fatty acids were observed among groups. Fecal metabolomics analysis further revealed that MSM hardly affected the metabolites. Overall, dietary supplementation with 0.2% MSM can improve the hair quality of kittens. Furthermore, 0.2∼0.4% of MSM had no detrimental effects on serum biochemistry, growth performance, gut microbiota, and metabolome, which supports the safety inclusion of MSM to a certain degree in feline diets. To the best of our knowledge, this is the first study to investigate the effects of MSM supplementation in cats.
... The exact metabolic fate of MSM is not fully understood, however, its tissue distribution and liver accumulation as well as formation by hepatic microsomes have been reported [40]. Studies in rats further demonstrate that up to 80% of MSM is excreted unchanged [41]. Here, we demonstrated that MSM caused no measurable changes in the expression of a panel of mouse hepatic Cyps. ...
Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we investigated the interaction potential between the cannabidiol-rich cannabis extract (CRCE) and methylsulfonylmethane (MSM), a popular dietary supplement, in the mouse model. For this purpose, 8-week-old male C57BL6/J mice received MSM-containing water (80 mg/100 mL) ad libitum for 17 days. During the last three days of treatment, mice received three doses of CRCE administered in sesame oil via oral gavage (123 mg/kg/day). Administration of MSM alone did not result in any evidence of liver toxicity and did not induce expression of mouse cytochrome P450 (CYP) enzymes. Administration of CRCE did produce significant (p < 0.05) increases in Cyp1a2, Cyp2b10, Cyp2c29, Cyp3a4, Cyp3a11, Cyp2c65, and Cyp2c66 messenger RNA, however, this effect was not amplified by MSM/CRCE cotreatment. Similarly, no evidence of liver toxicity was observed in MSM/CRCE dosed mice. In conclusion, short-term MSM/CRCE co-administration did not demonstrate any evidence of hepatotoxicity in the mouse model.
... There were no differences in MSM concentrations quantified in plasma and tissues of fresh and oxidized oil groups, except in abdominal skin. This suggests that dietary oxidation status may not affect MSM absorption and distribution, which matches with evidence from rat studies where MSM was shown to be well absorbed and distributed throughout the body (Otsuki et al., 2002;Magnuson et al., 2007) with a carrier independent unsaturable absorption from the small intestine (Wong et al., 2017). In agreement with our previous study regarding MSM distribution after oral gavage in broilers, the current data suggest that MSM supplemented via feed also has similar tissue distribution patterns. ...
Methylsulfonylmethane (MSM) is an organic, sulfur-containing compound widely used as a dietary supplement to improve joint health and treat arthritic pain. An experiment was conducted to study the effects of feeding 0.05% MSM to broilers exposed to diet-induced oxidative stress on tissue MSM distribution, growth performance, oxidative stress biomarkers, and immune responsivity. A total of 528 birds were allocated to 4 dietary treatments (fresh oil-no MSM, fresh oil-MSM, oxidized oil-no MSM, oxidized oil-MSM) as provided ad libitum to 11 replicate cages of 12 birds per treatment. Blood and tissue samples were collected to analyze MSM concentrations, and oxidative stress biomarkers including concentrations of thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), total glutathione, and glutathione peroxidase (GPx) and reductase (GR) activities. Additionally, blood samples collected at day 25 were used to quantify T-cell (TC) populations using flow cytometry. Overall, MSM was quantified in all tissues and plasma samples of MSM-treated groups at all time points. Oxidized oil reduced (P = 0.006) feed intake over the 21-d feeding period, but MSM did not affect growth equally across time points. No effects (P > 0.2) of MSM or oil type were observed on TC populations. In the presence of oxidized oil, MSM reduced (P = 0.013) plasma TBARS and increased (P = 0.02) liver GPx at day 21, and increased (P = 0.06) liver GR at day 7. Irrespective of dietary oil type, groups supplemented with MSM showed higher plasma TAC at day 7 (P = 0.023), liver GPx activity at day 21 (P = 0.003), and liver GR activity at day 7 (P = 0.004) compared with groups not receiving MSM. In conclusion, 0.05% dietary MSM supplementation partially protected birds from oxidative stress but did not affect immune cell profiles.
... The 8 h half-life of ingested inorganic sulfate is indicative of a similar rapid clearance [16] and is consistent with the regulation of a steady state pool of sulfate [17]. The present study provides novel findings for rapid carrier-independent, unsaturable intestinal absorption of MSM and how with chronic administration there is an increasing association of the sulfur moiety with proteins, which is consistent with how chronic feeding of MSM results in tissue retention [18]. ...
The principal dietary sources of sulfur, the amino acids methionine and cysteine, may not always be consumed in adequate amounts to meet sulfur requirements. The naturally occurring organosulfur compound, methylsulfonylmethane (MSM), is available as a dietary supplement and has been associated with multiple health benefits. Absorption of MSM by the small intestine and accumulation of the associated sulfur moiety in selected tissues with chronic (8 days) administration were evaluated using juvenile male mice. Intestinal absorption was not saturated at 50 mmol, appeared passive and carrier-independent, with a high capacity (at least 2 g/d-mouse). The 35S associated with MSM did not increase in serum or tissue homogenates between days 2 and 8, indicating a stable equilibrium between intake and elimination was established. In contrast, proteins isolated from the preparations using gel electrophoresis revealed increasing incorporation of 35S in the protein fraction of serum, cellular elements of blood, liver, and small intestine but not skeletal muscle. The potential contributions of protein synthesis using labeled sulfur amino acids synthesized by the gut bacteria and posttranslational sulfation of proteins by incorporation of the labeled sulfate of MSM in 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and subsequent transfer by sulfotransferases are discussed.
... There is limited formal safety data and no long-term assessment. However, MSM is rapidly excreted from the body 41,42 and animal toxicity studies of MSM showed only minor adverse events using doses of 1.5 g/kg and 2.0 g/kg of MSM for 90 days. This dose represents a human dose of 30e42 g/d, which is equivalent to 5e7 times the proposed maximum recommended human dose of 6 g/d 43 . ...
Objective Conventional treatment of osteoarthritis (OA) with non-steroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects and in view of the recent withdrawal of some cyclo-oxygenase-2 inhibitors, identifying safer alternative treatment options is needed. The objective of this systematic review is to evaluate the existing evidence from randomised controlled trials of two chemically related nutritional supplements, dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of OA to determine their efficacy and safety profile. Methods The electronic databases [Cochrane Library, Medline, Embase, Amed, Cinahl and NeLH (1950 to November 2007)] were searched. The search strategy combined terms: osteoarthritis, degenerative joint disorder, dimethyl sulfoxide, DMSO, methylsulfonylmethane, MSM, clinical trial; double-blind, single blind, RCT, placebo, randomized, comparative study, evaluation study, control. Inclusion and exclusion criteria were applied. Data were extracted and quality was assessed using the JADAD scale. Results Six studies were included [evaluating a total of 681 patients with OA of the knee for DMSO (N = 297 on active treatment); 168 patients for MSM (N = 52 on active treatment)]. Two of the four DMSO trials, and both MSM trials reported significant improvement in pain outcomes in the treatment group compared to comparator treatments, however, methodological issues and concerns over optimal dosage and treatment period, were highlighted. Conclusion No definitive conclusion can currently be drawn for either supplement. The findings from all the DMSO studies need to be viewed with caution because of poor methodology including; possible unblinding, and questionable treatment duration and dose. The data from the more rigorous MSM trials provide positive but not definitive evidence that MSM is superior to placebo in the treatment of mild to moderate OA of the knee. Further studies are now required to identify both the optimum dosage and longer-term safety of MSM and DMSO, and definitive efficacy trials.
... It was speculated that a small portion of the administered DMSO 2 might have been incorporated into keratin, a component of hair and nails. 153 Similarly, Magnuson et al. administrated a single oral dose of 35 S-DMSO 2 (500 mg/kg) to rats and revealed a recovery rate of 85.8% of the dose in urine and 3% in feces after 120 h, but no quantifiable levels of radioactivity were detected in any tissues. 154 Thus, DMSO 2 represents one of the major end products in the methionine degradation pathway. ...
There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS) and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expands our knowledge of microbial-derived metabolites, and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism.
... There is limited formal safety data and no long term assessment. However, MSM is rapidly excreted from the body [46,47] and animal toxicity studies of MSM showed only minor adverse events using doses of 1.5 g/kg and 2.0 g/kg of MSM for 90 days. This dose represents a human dose of 105-140 g/day, which is equivalent to 17-23 times the proposed maximum recommended human dose of 6 g/day [48]. ...
Dimethyl sulphoxide and methylsulfonylmethane are two related nutritional supplements used for symptomatic relief of osteoarthritis (OA). We conducted a meta-analysis to evaluate their efficacy in reducing pain associated with OA. Randomized or quasi-randomized controlled trials (RCTs), identified by systematic electronic searches, citation tracking and searches of clinical trial registries, assessing these supplements in osteoarthritis of any joint were considered for inclusion. Meta-analysis, based on difference in mean pain related outcomes between treatment and comparator groups, was carried out based on a random effect model. Seven potential trials were identified of which three RCTs, two DMSO and one MSM (total N = 326 patients) were eligible for inclusion. All three trials were considered high methodological quality. A significant degree of heterogeneity (χ2 = 6.28,
P = .043) was revealed. Two studies demonstrated statistically significant (but not clinically relevant) reduction in pain compared with controls; with one showing no group difference. The meta-analysis confirmed a non significant reduction of pain on visual analogue scale of 6.34 mm (SE = 3.49, 95% CI, −0.49, 13.17). The overall effect size of 1.82 was neither statistically nor clinically significant. Current evidence suggests DMSO and MSM are not clinically effective in the reduction of pain in the treatment of OA. No definitive conclusions can currently be drawn from the data due to the mixed findings and the use of inadequate dosing periods.
... We recently evaluated the absorption, distribution and excretion of orally administered MSM in rats, and found that [ 35 S]-MSM is rapidly absorbed, well distributed, and efficiently excreted from the body (Magnuson et al., in press). These data are in agreement with an earlier report of the rapid elimination of MSM (Otsuki et al., 2002). Recently, Kim et al. (2006) reported no difference in the incidence of minor adverse effects in arthritic patients consuming either placebo or 6 g MSM orally/day for 12 weeks. ...
Methylsulfonylmethane (MSM) is a metabolite of dimethyl sulfoxide, and occurs naturally at low levels in many foods. MSM has received wide attention as a dietary supplement to promote joint health. The objective of these studies was to determine the developmental toxicity potential of MSM when administered orally to pregnant rats during the period of major organogenesis and histogenesis. In a preliminary dose-finding study, distilled MSM microprill (i.e., microspherical pellets of MSM) was administered by oral gavage at dose levels of 0 (vehicle control), 50, 250, 500, and 1000 mg/kg/day to 8-9 sperm-positive female Sprague-Dawley rats/group/day on gestation days 6-20. No evidence of maternal or fetal toxicity was observed. For the definitive developmental study, four groups of 24-25 timed-bred primiparous female rats were administered 0, 50, 500, or 1000 mg MSM/kg/day via gavage on gestation days 6-20. Maternal feed consumption, body weight, body weight gain, uterus weight and corrected body weight/body weight gain were unaffected by treatment. No evidence of maternal toxicity, and no significant differences in litter viability, litter size, or litter body weight were detected. Fetal evaluations failed to show any biologically significant increase in the incidence of anomalies in the MSM treated groups, and no malformations were seen in any of the fetuses. No evidence of fetal mortality, alterations to growth, or structural alterations were observed in the fetuses of dams administered 50-1000 mg/kg/day. Therefore, under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 1000 mg/kg/day.
... There is limited formal safety data and no long-term assessment. However, MSM is rapidly excreted from the body 41,42 and animal toxicity studies of MSM showed only minor adverse events using doses of 1.5 g/kg and 2.0 g/kg of MSM for 90 days. This dose represents a human dose of 30e42 g/d, which is equivalent to 5e7 times the proposed maximum recommended human dose of 6 g/d 43 . ...
Objective:
Conventional treatment of osteoarthritis (OA) with non-steroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects and in view of the recent withdrawal of some cyclo-oxygenase-2 inhibitors, identifying safer alternative treatment options is needed. The objective of this systematic review is to evaluate the existing evidence from randomised controlled trials of two chemically related nutritional supplements, dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of OA to determine their efficacy and safety profile.
Methods:
The electronic databases [Cochrane Library, Medline, Embase, Amed, Cinahl and NeLH (1950 to November 2007)] were searched. The search strategy combined terms: osteoarthritis, degenerative joint disorder, dimethyl sulfoxide, DMSO, methylsulfonylmethane, MSM, clinical trial; double-blind, single blind, RCT, placebo, randomized, comparative study, evaluation study, control. Inclusion and exclusion criteria were applied. Data were extracted and quality was assessed using the JADAD scale.
Results:
Six studies were included [evaluating a total of 681 patients with OA of the knee for DMSO (N=297 on active treatment); 168 patients for MSM (N=52 on active treatment)]. Two of the four DMSO trials, and both MSM trials reported significant improvement in pain outcomes in the treatment group compared to comparator treatments, however, methodological issues and concerns over optimal dosage and treatment period, were highlighted.
Conclusion:
No definitive conclusion can currently be drawn for either supplement. The findings from all the DMSO studies need to be viewed with caution because of poor methodology including; possible unblinding, and questionable treatment duration and dose. The data from the more rigorous MSM trials provide positive but not definitive evidence that MSM is superior to placebo in the treatment of mild to moderate OA of the knee. Further studies are now required to identify both the optimum dosage and longer-term safety of MSM and DMSO, and definitive efficacy trials.
The loss of wild biodiversity has prompted the development of cryobanks, such as those of somatic cells. This is the reality of Pumas, wild felids of ecological importance that suffer from anthropogenic actions, population decline, and subsequent loss of genetic diversity. Somatic cell banks are a strategy for conserving population diversity. We compared different concentrations and types of intracellular cryoprotectants (dimethyl sulfoxide, DMSO; ethylene glycol, EG) associated with 0.2 M of sucrose (SUC) in the cryopreservation of the somatic cells of captive Pumas. The cells were cryopreserved by slow freezing with different solutions containing Dulbecco's modified Eagle's medium with 10% fetal bovine serum and varying concentrations of DMSO and EG in the absence or presence of SUC. The cells were analyzed for morphological characteristics, viability, proliferative activity, metabolic activity, and apoptosis levels. Cells maintained similar fusiform morphology before and after cryopreservation. There was no difference in viability, regardless of the reduction in the concentration and type of intracellular cryoprotectants and sucrose. Similarly, proliferative activity, metabolic activity, and apoptosis levels were not altered by the composition of the cryoprotectants. In summary, we demonstrate that reducing the concentration of DMSO or EG ensures adequate cryopreservation of Puma somatic cells, regardless of the presence of SUC.
Highlights
• Reducing the concentration of dimethyl sulfoxide or ethylene glycol ensures adequate cryopreservation of Puma somatic cells, regardless of sucrose.
• Apoptosis levels were not altered by the composition of the cryoprotectants.
• These results represent an advance for establishing somatic resource banks in zoos, aiming at conserving Pumas or phylogenetically close individuals.
Methylsulfonylmethane (MSM) is a naturally occurring organosulfur antioxidant. Based on its small size and unique physicochemical properties, MSM exhibits broad tissue distribution and pleiotropic effects. Animal toxicity studies suggest MSM is safe and nontoxic. Though the antioxidant mechanism is presently unclear, MSM has demonstrated the ability to protect against the activities of superoxide dismutase, catalase, and myeloperoxidase while also altering glutathione levels in numerous tissues. Through the modulation of antioxidant enzyme activities and redox hub cycling, MSM impacts cellular and tissue redox status, which can metabolically reprogram cells through redox-sensitive transcription factors. Alternatively, MSM may also affect membrane properties, specifically of mitochondria, thereby affecting reactive oxygen species production. By altering antioxidant potentials in various tissues including the brain, MSM may demonstrate unique immune modulatory properties that could prove useful to various pathological states.
Background: The application of cryopreservation in human and animal reproductive medicine has stimulated several studies about the effects of low temperatures and freezing processes on cells and tissues, in order to develop efficient protocols for gamete and embryo preservation. Moreover, cryopreservation is a fundamental tool for the establishment of animal germplasm banks, allowing the preservation of genetic material from several species and breeds or for further study and/or recovery of desirable characteristics. For the success of cryopreservation, the addition of an intracellular cryoprotectant agent in the freezing solution is indispensable. However, issues related to intracellular cryoprotectant agents used, e.g., their metabolism and potential toxicity, must be examined carefully so we can choose the cryoprotectant most suitable for a specific structure. Review: In this regard, this review introduces several aspects of cryopreservation, such as basic principles and methods used (slow freezing and vitrification), describing the fundamental steps of cryoprotectant agent's exposure, cooling, storage, thawing or warming and removal of the cryoprotectant agent. The addition of an intracellular cryoprotectant to the freezing solution is essential, but does not guarantee the success of the cryopreservation protocol, due to its toxic effect, which requires a perfect balance between cryoprotectant concentration, temperature and exposure time to the structure which will be cryopreserved. Some studies attribute the toxicity of these agents mainly to the secondary metabolites formed when the cell resumes its activity and gradually begins to metabolize the cryoprotectant agent. These secondary metabolites, such as lactate resulting from the degradation of propanediol and the production of oxalic acid after the catalysis of ethylene glycol, can interfere in a number ways on cellular homeostasis, resulting from an acid-base imbalance with cellular acidosis until the uncoupling of oxidative phosphorylation in the mitochondrial membrane, preventing the production of adenosine triphosphate. In addition, there are characteristics of tissue's formation and metabolic peculiarities inherent to each species, resulting in differences in optimal conditions required to maintain the biological properties of cells after thawing. Therefore, in addition to the knowledge about the chemical and biological characteristics of the most suitable cryoprotectant agent for a given species, it is also necessary to adjust the concentration and exposure time to it, allowing a more efficient preservation of various cell types. Conclusion: Cryopreservation is a valuable tool for female gametes preservation, providing support for several reproductive biotechnologies allowing safeguard the genetic material and facilitating its propagation. However, the success of this procedure depends on the proper use of a cryoprotectant agent, which application, although essential, can cause irreversible cell damage that can result in cellular death. Although there is no ideal cryoprotectant agent, able to protect completely the cell at low temperatures and also to be free of toxicity, it has been demonstrated that the cryoprotectants currently employed enabled the preservation of oocytes and ovarian tissue allowing the in vitro production of embryos and the restoration of fertility after transplantation.
Summary The process of cooling and cryopreservation of prawn embryos is a viable alternative for a continuous supply of larvae for freshwater prawn farming ponds. However, studies involving the application of those techniques as well as on toxicity of cryoprotectants in freshwater prawn embryos are scarce. Thus, this study aims to test the toxicity of methylic alcohol (MET), dimethyl sulfoxide (DMSO) and ethylene glycol (EG) on Macrobrachium amazonicum embryos. For the present experiment, pools of embryos were taken from 15 M. amazonicum females and were divided into three groups and tested in duplicate at concentrations of 10, 5, 3; 1, 0.5 or 0.1%. Toxicity tests were conducted for 24 h in Falcon® pipes to obtain the lethal concentration for 50% of the larvae (LC50). After the set period for testing, random samples of embryos were removed for morphological analysis under stereoscopic microscopes. Results were analysed using analysis of variance (ANOVA) and Tukey's test at a 5% significance level and Trimmed Spearman-Karber Analysis to determine LC50-24 h. DMSO toxicity tests revealed that 5% and 10% concentrations showed the highest toxicity and differed from the control (P ≤ 0.05), 24h-LC50 was 437.4 ± 14.4 µL. MET was less toxic among the tested cryoprotectants and concentrations did not allow the determination of its LC50-24h. For tests with EG, concentrations of 3, 5 or 10% solutions resulted in a 100% mortality to tested embryos; EG was the tested cryoprotectant with the highest toxicity, with an LC50-24h average of 81.91 ± 35.3 µl.
This study was conducted to compare the quality of the pork from finishing pigs that were fed diets containing different levels of methyl sulfonyl methane (MSM). A total of 135 crossbred pigs (LandracexYorkshirexDuroc) were fed either with a control commercial diet or the control diet supplemented with 300- and 500-ppm MSM for 158 d. The pigs were slaughtered at approximately 110 kg live weight and were transported to the local slaughterhouse for electrical stunning followed by exsanguination. After the slaughter, the pork muscles were dissected from each carcass, placed in wrap package bags, and stored for 8 d at 4°C. The TB ARS values of the pigs that were fed MSM diets were significantly lower (p<0.05) compared with those of the pigs that were fed with non-supplemented diets. The Na, Mg, and Ca contents of the dietary MSM were significantly lower (p<0.05) than those of the non-supplemented diets, but the Fe, Cu, and Zn contents of the dietary MSM were significantly higher (p<0.05) than those of the non-supplemented diets, and the increased level of MSM supplementation resulted in higher sulfur contents. There was no difference among the diets in terms of amino acid content. The dietary supplementation with MSM, however, led to increased saturated fatty acid and decreased unsaturated fatty acid (%) in the pork muscles (p<0.05). The sensory panelists recorded greater marbling and overall acceptability scores in the samples with 500-ppm-MSM dietary supplementation (p<0.05). These data suggest that supplementing pig diets with MSM can improve the quality of the pork and can enhance the eating quality because the sensory panels found that the pork from pigs that were fed an MSM-supplemented diet had better sensory characteristics.
Two types of onions cultivated with different methods of sulfur application (designated as S-1 and S-2) were examined for their physicochemical and sensory properties, and then compared with onions without sulfur application as a control. During cultivation, dietary sulfur methylsulfonylmethane (MSM) was sprayed on the leaves twice starting at 2 months before harvest, with one month intervals for S-1. For S-2, the MSM was applied once onto surface soils before sowing, and then once again on the leaves at 2 months before harvest. Thiosulfinate, a major sulfur-containing compound in onions, increased in the order of control, S-1, and S-2, without noticeable differences in the strength of spicy hot taste and flavor. The S-2 onions demonstrated a total reducing capacity three times higher than control and S-1 did. It indicates that the application of sulfur would positively affect the quality of onions under the condition where sufficient time is given for soil mineralization.
Methylsulfonylmethane (MSM), also known as dimethyl sulfone and methyl sulfone, is an organic sulfur-containing compound that occurs naturally in a variety of fruits, vegetables, grains, and animals, including humans. In the present study, we demonstrated the anti-inflammatory effects of MSM in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. MSM significantly inhibited the release of nitric oxide and prostaglandin E(2) by alleviating the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW264.7 cells. Furthermore, the levels of interleukin-6 and tumor necrosis factor-alpha were decreased by MSM treatment in cell culture supernatants. Further study indicated that the translocation of the p65 subunit of nuclear factor (NF)-kappaB to the nucleus was inhibited by MSM treatment in LPS-stimulated RAW264.7 cells, in which it helped block degradation of inhibitor of NF-kappaB. In addition, in vivo studies demonstrated that topical administration of MSM at 500-1250 microg/ear resulted in similar inhibitory activities in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Collectively, theses results indicate that MSM inhibits LPS-induced release of pro-inflammatory mediators in murine macrophages through downregulation of NF-kappaB signaling.
An expedient two-step synthesis of [13C2]DMSO, starting from commercially available [13C]methyl iodide, is described. The product obtained in 57% yield is of high chemical (≥ 99%) and isotopic purity (= 98% 13C2, 2% 13C1), as jugded by NMR-spectroscopy and a GC-MS-assay.
Dietary products, and uses comprising methylsulfonylmethane
- Rj Herschler
Herschler RJ. Dietary products, and uses comprising methylsulfonylmethane. US Patent 4,863,748, 1989.
Dietary, and pharmaceutical uses of methylsulfonylmethane, and compositions comprising it
- Rj Herschler
Herschler RJ. Dietary, and pharmaceutical uses of methylsulfonylmethane, and compositions comprising it. US Patent 4,514,421, 1985.
Methylsulfonylmethane in dietary products
- Rj Herschler
Herschler RJ. Methylsulfonylmethane in dietary products. US Patent 4,616,039, 1986.
Use of methylsulfonylmethane to treat parasitic infections
- Rj Herschler
Herschler RJ. Use of methylsulfonylmethane to treat parasitic infections. US Patent 4,514,135, 1990.
Methylsulfonylmethane, and methods of use
- Rj Herschler
Herschler RJ. Methylsulfonylmethane, and methods of use. US Patent 4,296,130, 1981.