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Toxicity of methylsulfonylmethane in rats

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Abstract

Methylsulfonylmethane (MSM) is a popular dietary supplement used in a variety of conditions including pain, inflammation, allergies, arthritis, parasitic infections and the maintenance of normal keratin levels in hair, skin and nails. Despite its popularity, there is little published toxicology data on MSM. The objective of this study was to evaluate the acute and subchronic toxicity of MSM in rats at a dose five to seven times the maximum recommended dose in humans. MSM administered in a single gavage dose of 2 g/kg resulted in no adverse events or mortality. MSM administered as a daily dose of 1.5 g/kg for 90 days by gavage resulted in no adverse events or mortality. Necropsy did not reveal any gross pathological lesions or changes in organ weights. Renal histology of treated animals was normal. It is concluded that MSM is well tolerated in rats at an acute dose of 2 g/kg and at a subacute chronic dose of 1.5 g/kg.
... The active substance doses specified in the publications were administered in the intervention groups. Since Tendoflex® contains more than one active substance, the treatment given has been decided by looking at these active ingredients one by one [5,[16][17][18][19]. In one study, bromelain was found beneficial at a dose of 30 mg/kg for tendon injury [5]. ...
... In another study, it was reported that L-arginine was used in rats at doses of 30-60 mg/kg [18]. In another study, methyl sulfonyl methane was used at a dose of 50 mg/kg [19]. In the light of all these studies, 1 capsule of Tendoflex® was weighed to correspond to a 2.5 kg rat weight. ...
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Aim: This experimental animal study aimed to investigate the effects of Tendoflex® (a polytendon complex) and St. John's wort oil (Hypericum perforatum) on healthy Achilles tendons in rats. Material and Method: Twenty Wistar albino rats weighing 250-350 g were randomly allocated into four groups. In Group A, Tendoflex® capsule per 2.5 kg/ day was administered orally via gavage. In Group B, Hypericum perforatum 300mg/kg/day was given orally via gavage. In Group C, Tendoflex® and Hypericum perforatum were given orally via gavage at the doses mentioned above. In Group D, no intervention was done to the control group. After four weeks, all rats were sacrificed and biomechanical tests of the Achilles tendon and histological examinations were performed. Results: Histological results revealed a significant difference between the groups regarding Type-1 and Type-3 immunopositivity in the Achilles tendon tissues (p <0.05). Immune-positivity values were high in group B, moderate in group C, mild in group A and insignificant in group D. The highest top tendon strengths in the biomechanical tests were recorded in the Hypericum perforatum and mix groups at the fourth week (83.75±16.1N and 81.875±9.7 N, respectively) followed by the Tendoflex® group (66.875±7.5 N). On the other hand, the lowest tendon strengths were obtained in the control group (54.375±7.1N). Discussion: Tendoflex® and Hypericum perforatum increased the Achilles tendon tensile strength in rats. This result may be related to the fact that Type-1 and Type-3 collagen immunity was higher in all groups compared to the control group. Tendoflex® and Hypericum perforatum can be used to prevent tendon rupture or to avoid re-rupture in patients undergoing tendon repair.
... Tendoflex ® preparation contains 125 mg of methyl sulfonyl methane, 100 mg of L-arginine, 75 mg of bromelain, 60 mg of vitamin C (L-ascorbic acid), 50 mg of rutin, and 40 mg of collagen type I. Since Tendoflex ® contains more than one active ingredient, the amount to be given to the rats was decided by checking these active ingredients separately. [12][13][14][15][16] Bromelain, L-arginine, and methyl sulfonyl methane were used as reference for the dose calibration according to the whole capsule. In a study on bromelain, a dose of 30 mg/kg was shown to be beneficial on tendon damage. ...
... [14] In another study, methyl sulfonyl methane was used at a dose of 50 mg/kg. [13] One tablet containing 125 mg of methyl sulfonyl methane was used for each 2.5 kg of a rat to use 50 mg of methyl sulfonyl methane per kg. In the light of all these studies, one capsule of Tendoflex ® was weighed to correspond to 2.5-kg weight of a rat and given by gavage daily according to the weight of the animal. ...
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Objectives: This experimental study aims to examine the effects of Tendoflex® and Hypericum perforatum on tendon healing in rat models undergoing iatrogenic Achilles tendon rupture and similar surgical treatments. Materials and methods: Eighty Wistar albino rats weighing 250 to 350 g were randomly divided into four groups. Group A: Tendoflex® was administered orally as 1 capsule/2.5 kg daily by gavage. Group B: Hypericum perforatum was administered orally as 300 mg/kg daily by gavage. Group C: Tendoflex® and Hypericum perforatum were co-administered orally by gavage at the prespecified doses. Group D: No medication was given to the control group. Five rats from each group were sacrificed weekly, and the tissue samples were examined histologically, followed by the biomechanical tests of the Achilles tendon. Results: In the mechanical testing, pulling forces were superior in all intervention groups and in all weeks over the control group. In particular, in the early periods (Weeks 1, 2, and 3), the mixed group showed the most favorable results, followed by the Hypericum perforatum group (p=0.010, p=0.591, and p=0.130, respectively). The most favorable collagen type I and type III expression values were found in the mixed and Hypericum perforatum groups at Weeks 2 and 3, respectively (p=0.025 and p=0.018). In the immunohistochemical and Western Blot examinations, extreme collagen type I and type III expression were detected in the mixed and Hypericum perforatum groups at Weeks 2, 3, and 4. Conclusion: Tensile strength of the Achilles tendon increased by using Hypericum perforatum and Tendoflex® following rupture and repair of the Achilles tendon in rats. The combined use of these two agents yielded the most favorable mechanical and histological results, particularly in the early period. This result may be related to the higher level of collagen type I and type III immunity in all groups, compared to the control group.
... These organic compounds are biosynthesised in the large intestines by bacterial fermentation of dietary fibre [28]. Similarly, the dimethyl sulfone amount was higher in satiated than in hungry rats, which is a metabolite of dimethyl sulfoxide that is found in many foods, including grains and raw vegetables, both of which are regularly fed to our rats [29]. As hungry rats did not have access to food for 16 h, this fasting condition may have been reflected by their low abundance of dimethyl sulfone. ...
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When individuals exchange helpful acts reciprocally, increasing the benefit of the receiver can enhance its propensity to return a favour, as pay-offs are typically correlated in iterated interactions. Therefore, reciprocally cooperating animals should consider the relative benefit for the receiver when deciding to help a conspecific. Norway rats (Rattus norvegicus) exchange food reciprocally and thereby take into account both the cost of helping and the potential benefit to the receiver. By using a variant of the sequential iterated prisoner’s dilemma paradigm, we show that rats may determine the need of another individual by olfactory cues alone. In an experimental food-exchange task, test subjects were provided with odour cues from hungry or satiated conspecifics located in a different room. Our results show that wild-type Norway rats provide help to a stooge quicker when they receive odour cues from a hungry rather than from a satiated conspecific. Using chemical analysis by gas chromatography-mass spectrometry (GC-MS), we identify seven volatile organic compounds that differ in their abundance between hungry and satiated rats. Combined, this “smell of hunger” can apparently serve as a reliable cue of need in reciprocal cooperation, which supports the hypothesis of honest signalling.
... MSM is a popular dietary supplement that is used for various reasons, including the maintenance of normal keratin levels in the hair, skin, and nails. 28 Keratin provides intra-and intermolecular hydrogen bonds and large amounts of the sulfur-containing amino acid cysteine required for the disulfide bridges. Extensive disulfide bonding contributes to the insolubility of keratins and thermally stable crosslinking that imparts significant strength and rigidity to hair and nail structures. ...
Chapter
Sulfur is a chemical element with the symbol S and atomic number 16. It is a multivalent, nonmetallic element found in large amounts in the human body. It is the third most abundant mineral based on the percentage of total body weight, representing 0.25% of the average body weight, slightly higher than sodium [1]. Sulfur-containing compounds are found in all body cells and are indispensable for life, but sulfur in the human body is almost always found in the form of organosulfur compounds or metal sulfides. Most of the 150–170 g of sulfur in the human body are distributed in sulfite structural proteins, and a small percentage is found within all cells [2].
Article
Background Multi-drug-resistant bacterial infections, which have become a global threat, lack effective treatments. The discoveries of non-antibiotics with different modes of antibacterial action, such as methylsulfonylmethane (MSM), are a promising new treatment for multi-drug-resistant pathogens. Methods We constructed a mouse peritonitis infection model to evaluate the effects of MSM against methicillin-resistant Staphylococcus aureus (MRSA) infection. The time-kill kinetics of MSM against MRSA and the effect of MSM on the integrity of bacterial cell membrane were measured. Viability effects of MSM on THP1 cells were performed by CCK-8 cytotoxicity assay. Systematic inflammatory factor levels of mice were detected using ELISA. The immune response of peritoneal macrophages during MRSA-infection was evaluated using RNA sequencing. Gene Ontology function, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and correlation analyses were applied to analysis RNA sequencing data. RT-qPCR, western blotting and flow cytometry were performed to analysis the gene and protein expression levels of macrophages. Results In in vitro experiments, MSM did not show significant killing effects on the growth of MRSA directly and did not destroy bacterial membrane integrity. MSM also displayed no significant effects on the proliferative capacity of THP1 cells. However, MSM treatment protected mice against a lethal dose MRSA-infection and decreased systemic inflammation. MSM upregulated metabolic pathway in peritoneal macrophages, especial glycolysis, during MRSA infection. MSM increased the expression of M2 markers (such as Arg1), promoted phosphorylation of STAT3 (which regulates M2 polarization), and decreased the expression of M1 markers in peritoneal macrophages. Additionally, MSM treatment increased the expression of H3K18 lactylation specific target genes, including Arg1. GNE-140, the LDHA-specific inhibitor of glycolysis, blocked the MSM-induced Arg1 expression in this disease model. Conclusions MSM protects against MRSA infection through immunomodulation. MSM promotes the expression of Arg1 by lactate-H3K18la pathway to control macrophage to M2 polarization; it firstly provides therapeutic potential for drug-resistant infections and sepsis.
Article
Inspired by Locard's exchange principle, which states "every contact leaves a trace", a trace residue sampling strategy has been developed for the analysis of discarded drug packaging samples (DPS), as part of an early warning system for illicit drug use at large public events including music/dance festivals. Using direct analysis in real time/mass spectrometry and tandem mass spectrometry, rapid and high-throughput identification and characterization of a wide range of illicit drugs and adulterant substances was achieved, including in complex polydrug mixtures and at low relative ion abundances. A total of 1362 DPS were analyzed either off-site using laboratory-based instrumentation or on-site and in close to real time using a transportable mass spectrometer housed within a mobile analytical laboratory, with each analysis requiring less than 1 min per sample. Of the DPS analyzed, 92.2% yielded positive results for at least one of 15 different drugs and/or adulterants, including cocaine, MDMA, and ketamine, as well as numerous novel psychoactive substances (NPS). Also, 52.6% of positive DPS were found to contain polydrug mixtures, and a total of 42 different drug and polydrug combinations were observed throughout the study. For analyses performed on-site, reports to key stakeholders including event organizers, first aid and medical personnel, and peer-based harm reduction workers could be provided in as little as 5 min after sample collection. Following risk assessment of the potential harms associated with their use, drug advisories or alerts were then disseminated to event staff and patrons and subsequently to the general public when substances with particularly toxic properties were identified.
Article
Objective To describe a case of the successful management of hypernatremia and multiple organ dysfunction syndrome secondary to joint supplement toxicity in a dog. Case summary A 6‐year‐old neutered male Dachshund was presented for severe hypernatremia and neurological abnormalities after ingestion of a large quantity of joint supplements. The patient developed evidence of multiple organ dysfunction in the form of increased hepatocellular enzymes, prolongation of prothrombin and partial thromboplastin times, azotemia, and thrombocytopenia. Treatment was successful at correcting the hypernatremia and restoring neurological function, and organ dysfunction was successfully managed. Following multiple days of hospitalization and aggressive supportive care, the patient survived to discharge. New or unique information provided This case report describes the successful management and survival of multiple organ dysfunction associated with joint supplement toxicity. It also serves to highlight the potential for joint supplement overdose in veterinary patients, which is currently believed to be underrecognized.
Chapter
Currently, more than 46 million adults in the United States suffer from some form of arthritis. Arthritis is also prevalent in other species, including canine and equine. Among all forms of arthritis, osteoarthritis (OA) is the most common form, afflicting nearly 27 million adults. The other common form of arthritis is rheumatoid arthritis. Among animal species, canine and equine are more prone to arthritis than other species. A large number of factors, such as aging, excessive exercise, obesity, genetic predisposition, immune disorders, poor nutrition, injury, and infection, can lead to OA. Presently, the use of nutraceuticals appears to be a good option to treat or manage OA, because they are taken orally, well-tolerated, and safe. However, some nutraceuticals exert adverse effects. This chapter describes, in brief, the characteristics of OA, pathophysiology of OA, and efficacy, safety, and toxicity of some commonly used nutraceuticals.
Chapter
This chapter deals with the various of forms of therapies given for treating equine lameness. The treatment types include systemic and parenteral therapies, topical and local therapies, intrasynovial therapies, intralesional therapies, oral and nutritional therapies, corrective shoeing and therapeutic shoeing, acupuncture treatments, manual therapies, and rehabilitation and physical therapy. Systemic administration of medications to treat musculoskeletal diseases in the horse mainly encompasses intravenous nonsteroidal anti‐inflammatory drugs (NSAIDS), intramuscular polysulfated glycosaminoglycans, and intravenous hyaluronan. The most commonly used IV NSAIDs are phenylbutazone and flunixin meglumine. The need for systemic NSAID therapy can be reduced and associated edema and tissue damage minimized with effective use of topical therapy. Equine practitioners currently have several options available to treat intrasynovial inflammation. Intrasynovial therapies, specifically corticosteroids, are used frequently in horses to minimize or control pain associated with synovitis and osteoarthritis.
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ALL models of natural processes for the transfer of sulphur on a global scale1–4 require some volatile or gaseous sulphur compound to complete the cycle by providing a vehicle for the transfer of sulphur from the sea through the air to the land surfaces. In the past, this role has been assigned to H2S and an average atmospheric concentration of 2×10−10 by volume satisfied the mass transfer needs of the models. Attempts to detect the presence of these concentrations of H2S have always failed and, more important, the ocean surface waters are much too oxidizing to permit the existence of H2S at concentrations sufficient to sustain an atmospheric equilibrium concentration of 2×10−10 by volume. Many elements form volatile methyl derivatives; Challenger5 reported that many living systems produced dimethyl sulphide (DMS), and that prominent among them were marine algae. Here we suggest that DMS is the natural sulphur compound which fills the role originally assigned to H2S; that of transferring sulphur from the seas through the air to land surfaces.
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Methionine, an essential amino acid, and cysteine are the major sulfur-containing amino acids in the body and both are thought to be synthesized predominantly in plants and micro-organisms. Methylsulfonylmethane (MSM) is a natural constituent of the environment in which it is found in plants, in milk and urine of both bovines and humans, is a normal oxidation product of dimethyl sulfoxide (DMSO) also in the natural environment and may be part of the natural global sulfur cycle. To determine whether sulfur from methylsulfonylmethane (MSM) is incorporated into sulfur amino acids, I fed 35S-MSM to guinea pigs. 35S was incorporated into peptidyl methionine and cysteine of guinea pig serum proteins. The specific activity of 35S-methionine was 30% greater than for 35S-cysteine, suggesting a precursor-product relationship. Total specific activity of serum proteins was increased by only 30% with a 100% increase of administered 35S-MSM, suggesting a limiting step in synthesis. Approximately 1% of the radioactivity was recovered in serum proteins, none in the feces and most was excreted in the urine. Microorganisms of intestinal lumen may be responsible for the incorporation of the 35S of MSM into sulfur amino acids. MSM may provide a source of sulfur for essential animal methionine by mechanisms not yet elucidated in either animals or micro-organisms.
The Miracle of MSM: The Natural Solution for Pain
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Methylsulfonylmethane (MSM): a double-blind study of its use in degenerative arthritis
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