[Effect of 6-month S-methylmethionine intake on the quality of life and dyspepsia symptoms in patients with chronic gastritis].

S-methylmethionine (methylmethionine sulfonium chloride), better known as vitamin U, is a metabolic substrate that affects many metabolic processes in the human organism. Since its discovery, a large number of studies has been produced demonstrating its safety and effectiveness in various diseases, especially in diseases of the gastrointestinal tract. The purpose of the study was to evaluate the effect of methylmethionine sulfonium chloride (vitamin U) intake on the symptoms of dyspepsia and the quality of life of patients with chronic gastritis. Material and methods. The study included 37 patients (21 men and 16 women) aged 35-60 years with chronic gastritis of various etiologies. After inclusion in the study, all patients were prescribed S-methylmethionine at a dose of 300 mg per day. Clinical manifestations of dyspepsia were assessed using the GSRS questionnaire (Gastrointestinal Symptom Rating Scale), quality of life was assessed using the SF 36 questionnaire. The survey was conducted before the start of the therapy, after 3 and 6 months of complex diet therapy. Results. The most pronounced manifestations were dyspeptic (from 3 to 9 points) and diarrheal syndromes (from 2 to 5 points). Other indicators of the GSRS scale did not exceed 4 points. The total score was 15 points. By the 3rd month of therapy, there was a statistically significant decrease in the total score to 9 points (p<0.05). By the 6th month of therapy, the total GSRS score averaged 5.5 points (p<0.05). According to the SF 36 questionnaire, by the end of the 3rd month of therapy, indicators such as PF - physical functioning, BP - Bodily pain and SF - social functioning improved. By the end of the 6th month of therapy, several other indicators also improved (RP - role-physical functioning, GH - general perception of health, VT - viability, RE - Role-Emotional; MH - mental health) (p<0.05). Conclusion. The study showed that the appointment of dietary supplements containing methylmethionine sulfonium chloride at a dose of 300 mg per day helps to reduce the severity of dyspeptic symptoms in patients with chronic gastritis and their quality of life.

The protective effect of vitamin U on pentylenetetrazole-induced brain damage in rats.

Pentylenetetrazole (PTZ) is preferred for experimental epilepsy induction. PTZ damages brain and other organs by elevating oxidative substances. Vitamin U (Vit U) is sulfur derivative substance that proved to be an excellent antioxidant. The current study was intended to determine the protective role of Vit U on PTZ-induced brain damage. Male Sprague-Dawley rats were separated into four groups. The Control group (Group I), was given saline for 7 days intraperitoneally (i.p); Vit U (Group II) was given as 50 mg/kg/day for 7 days by gavage; PTZ was injected into animals (Group III) at a single dose of 60 mg/kg, by i.p; PTZ + Vit U group (Group IV) was administered PTZ and Vit U in same dose and time as aforementioned. After the experiment was terminated, brain tissues were taken for the preparation of homogenates. In the PTZ group, glutathione and lipid peroxidation levels, alkaline phosphatase, myeloperoxidase, xanthine oxidase, acetylcholine esterase, antioxidant enzyme activities, total oxidant status, oxidative stress index, reactive oxygen species, and nitric oxide levels were increased. However, total antioxidant capacity was decreased in the PTZ group. Vit U ameliorated these effects in the PTZ-induced brain damage. Consequently, we can suggest that Vit U protected brain tissue via its antioxidant feature against PTZ kindling epilepsy.

Gastroprotective effect of vitamin U in D-galactosamine-induced hepatotoxicity.

Galactosamine (GalN) is a well-known agent for inducing viral hepatitis models in rodents, but it can cause toxicity on different organs. Vitamin U (Vit U) has been proved as a powerful antioxidant on many toxicity models. The present study was designed to investigate the protective effects of Vit U on GalN-induced stomach injury. Rats were divided into four groups as follows: control (group I), Vit U given animals (50 mg/kg per day; group II), GalN administered animals (500 mg/kg at a single dose; group III), GalN + Vit U given animals (at the same dose and time, group IV). At the end of the 3rd day, animals were killed, and stomach tissues were taken. They were homogenized and centrifuged. In comparison to the control group, glutathione, total antioxidant capacity levels, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and Na+ /K+ -ATPase activities of GalN group were found to be decreased. On the contrary, lipid peroxidation, advanced oxidized protein products, hexose-hexosamine, fucose, sialic acid, reactive oxygen species levels, as well as the activities of myeloperoxidase, xanthine oxidase, and lactate dehydrogenase were elevated. Administration of Vit U reversed these abnormalities in the GalN group. It can be concluded that Vit U exerts its unique antioxidant effect and prevents GalN-induced gastric damage.

POSSIBILITIES OF COMPLEX CORRECTION OF MORPHOLOGICAL GASTRODUODENAL CHANGES WITH COMORBIDITY OF CHRONIC PANCREATITIS AND CHRONIC H. PYLORI - GASTRITIS.

OBJECTIVE: The aim: To investigate the efficacy of Doctovit, a combination of dexpanthenol (provitamin B5) and methylmethionine (vitamin U), in the treatment of patients with chronic pancreatitis in combination with chronic erosive gastritis associated with H. pylori by studying the dynamics of stomach lining morphological changes. PATIENTS AND METHODS: Materials and methods: Forty-five outpatients with CP and H.pylori CG were examined. The degree of excretory insufficiency of the pancreas was determined by the level of fecal α-elastase-1. At the beginning of the study and two months after the treatment has started, esophagogastroduodenoscopy + urease test for H. pylori + biopsy from 5 sites with histological examination has been performed. RESULTS: Results: It was found that a significant decrease in lymphohistiocytic infiltration of stomach lining, restoration of the structure of glands which have not undergone atrophy, increased focal hyperplasia (proliferation) of the glandular epithelium as signs of morphological restoration of the epithelium, reduction of epithelial dysplasia signs against the complete absence of positive dynamics of epithelial dysplasia in the group of patients receiving standard treatment of CP and CG, are clear and reliable signs of the effectiveness of vitamin Doctovit in complex therapy of CG associated with H.pylori, which indicate the feasibility of using the medicine to restore SL, which is the basis for effective carcinoprevention. CONCLUSION: Conclusions: The effectiveness of both treatment complexes in the correction of exocrine insufficiency of the pancreas by the dynamics of fecal α-elastase-1 was proved and which was statistically significantly higher when using the program with the inclusion of Doctovit: respectively 28.12% vs. 20.74% (p< 0.05). The total dynamics of morphological state improvement of stomach lining in the 1st group of patients was 0.9 points against 1.6 points in the 2nd group of patients, which was 17% and 32%, respectively (p <0.05), which activates clinical data on the effectiveness and feasibility of using a combination of dexpanthenol and methylmethionine according to the suggested scheme in the treatment of patients with chronic pancreatitis in comorbidity with H. pylori erosive CG.

Vitamin U prevents valproic acid-induced liver injury through supporting enzymatic antioxidant system and increasing hepatocyte proliferation triggered by inflammation and apoptosis.

The aim of this study was to investigate the cellular mechanisms that cause valproic acid (VPA)-induced liver damage and the therapeutic effect of Vitamin U (Vit U) on these mechanisms. Female Sprague Dawley rats were randomly divided into four groups: intact control animals, animals that received Vit U (50 mg/kg/day), animals given VPA (500 mg/kg/day), and animals given both VPA and Vit U. The rats in the Vit U + VPA group were administered Vit U by gavage an hour before VPA administration every day for 15 days. Liver tissues were evaluated through histopathological, biochemical, immunohistochemical, and Western blotting techniques. Administration of Vit U with VPA resulted in (i) prevention of histopathological changes caused by VPA; (ii) blockage of the decrease in catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities; prevention of the elevation in gamma-glutamyl transferase (GGT) activity and advanced oxidation protein products (AOPP) level; (iii) increased in the levels of interleukin-1 beta (IL-1ß), active caspase-3, and cytoplasmic cytochrome c; (iv) increase in cleaved poly (ADP-ribose) polymerase (PARP) level and decrease in LC3B (II/I) ratio; (v) increase in the number of proliferating cells nuclear antigen (PCNA) positive hepatocytes. These findings show that Vit U prevents liver damage caused by VPA through increasing the antioxidant enzyme capacity and hepatocyte proliferation by triggering inflammation and apoptosis. These findings suggest that Vit U provides its protective effects against VPA-induced liver damage by stimulating homeostasis and regeneration.

Increased Intestinal Absorption of Vitamin U in Steamed Graviola Leaf Extract Activates Nicotine Detoxification.

Graviola leaves contain much vitamin U (vit U), but their sensory quality is not good enough for them to be developed as food ingredients. Addition of excipient natural ingredients formulated alongside vit U as active ingredients could enhance not only its sensory quality but also its bioavailability. The objectives of this study were to measure the bioaccessibility and intestinal cellular uptake of bioactive components, including rutin, kaempferol-rutinoside, and vit U, from steamed extract of graviola leaves (SGV) and SGV enriched with kale extract (SGK), and to examine how much they can detoxify nicotine in HepG2 cells. The bioaccessibility of vit U from SGV and SGK was 82.40% and 68.03%, respectively. The cellular uptake of vit U in SGK by Caco-2 cells was higher than that in SGV. Cotinine content converted from nicotine in HepG2 cells for 120 min was 0.22 and 0.25 µg/mg protein in 50 µg/mL of SGV and SGK, respectively, which were 2.86 and 3.57 times higher than the no-treatment control. SGK treatment of HepG2 cells upregulated CYP2A6 three times as much as did that of SGV. Our results suggest that graviola leaf extract enriched with excipient ingredients such as kale could improve vit U absorption and provide a natural therapy for detoxifying nicotine.

[S-methylmethionin (vitamin U): experimental studies and clinical perspective].

Vitamin-like compound S-methyl-L-methionine (SMM, historically called vitamin U) is a metabolic agent, affects metabolic processes, which causes a wide variety of effects. The data of the studies demonstrating gastroprotective effect, hypolipidemic and antioxidant effect, participation in regulation of adipocyte function, homocysteine exchange are presented. SMM is involved in all methylation reactions in which another activated form of methionine, S-adenosylmethionine, normally participates. The results of the observed studies indicate a possible expansion of the clinical use of S-methylmethionine.

The effect of vitamin U on the lung tissue of pentyleneterazole-induced seizures in rats.

The aim of this study is to investigate the therapeutic effects of vitamin U (Vit U) on lung tissue of pentyleneterazole (PTZ)-induced seizures in rats. Sprague Dawley male rats were randomly divided into four groups as follows: control (0.9% NaCl given, intraperitoneally); Vit U (50 mg/kg/day, for 7 days by gavage); PTZ; (60 mg/kg one dose, intraperitoneally); and PTZ + Vit U (in same dose and time). At the end of the experiment, lung tissues were taken and examined biochemically and cytologically. Lipid peroxidation (LPO), glutathione (GSH), sialic acid (SA), and nitric oxide (NO) levels, and superoxide dismutase (SOD) and catalase (CAT) activities were determined in lung homogenates. Imprinted lung samples were stained with May Grunwald-Giemsa stain and microscopically examined for the presence of collagen fibers, macrophage, leucocyte, and epithelial cells. PTZ administration significantly increased GSH level and CAT activity and significantly decreased SOD activity compared to the control group. Vit U administration significantly increased GSH level and CAT activity compared to the control group. GSH and NO levels significantly decreased in PTZ + Vit U group compared to the PTZ group. In cytologic analysis, increased collagen fibers, macrophages, leucocytes, and epithelial cells were observed in PTZ group compared to the control group, and Vit U administration decreased these cytological parameters compared to the PTZ group. The findings of this study support the possible protective role of using Vit U as an add-on therapy in order to prevent lung tissue injury which may occur during seizures in epilepsy.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-L-Methionine.

S-methyl-L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties.

The aim of present study was to investigate the effect of vitamin U (vit U, S-methylmethionine) on oxidative stress, inflammation, and fibrosis within the context of valproic acid (VPA)-induced renal damage. In this study, female Sprague Dawley rats were randomly divided into four groups: Group I consisted of intact animals, group II was given vit U (50 mg/kg/day, by gavage), group III was given VPA (500 mg/kg/day, intraperitonally), and group IV was given VPA + vit U. The animals were treated by vit U 1 h prior to treatment with VPA every day for 15 days. The following results were obtained in vit U + VPA-treated rats: (i) the protective effect of vit U on renal damage was shown by a significant decrease in histopathological changes and an increase in Na(+)/K(+)-ATPase activity; (ii) anti-oxidant property of vit U was demonstrated by a decrease in malondialdehyde levels and xanthine oxidase activity and an increase in glutathione levels, catalase and superoxide dismutase activities; (iii) anti-inflammatory property of vit U was demonstrated by a decrease in tumor necrosis factor-α, interleukin-1ß, monocyte chemoattractant protein-1 levels, and adenosine deaminase activity; (iv) anti-fibrotic effect of vit U was shown by a decrease in transforming growth factor-ß, collagen-1 levels, and arginase activity. Collectively, these data show that VPA is a promoter of inflammation, oxidative stress, and fibrosis which resulted in renal damage. Vit U can be proposed as a potential candidate for preventing renal damage which arose during the therapeutic usage of VPA.

Vitamin U, a novel free radical scavenger, prevents lens injury in rats administered with valproic acid.

Valproic acid (2-propyl-pentanoic acid, VPA) is the most widely prescribed antiepileptic drug due to its ability to treat a broad spectrum of seizure types. VPA exhibits various side effects such as organ toxicity, teratogenicity, and visual disturbances. S-Methylmethioninesulfonium is a derivative of the amino acid methionine and it is widely referred to as vitamin U (Vit U). This study was aimed to investigate the effects of Vit U on lens damage parameters of rats exposed to VPA. Female Sprague Dawley rats were divided into four groups. Group I comprised control animals. Group II included control rats supplemented with Vit U (50 mg/kg/day) for 15 days. Group III was given only VPA (500 mg/kg/day) for 15 days. Group IV was given VPA + Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals which were fasted overnight were killed. Lens was taken from animals, homogenized in 0.9% saline to make up to 10% (w/v) homogenate. The homogenates were used for protein, glutathione, lipid peroxidation levels, and antioxidant enzymes activities. Lens lipid peroxidation levels and aldose reductase and sorbitol dehydrogenase activities were increased in VPA group. On the other hand, glutathione levels, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and paraoxonase activities were decreased in VPA groups. Treatment with Vit U reversed these effects. This study showed that Vit U exerted antioxidant properties and may prevent lens damage caused by VPA.

Inhibitory Effect of Vitamin U (S-Methylmethionine Sulfonium Chloride) on Differentiation in 3T3-L1 Pre-adipocyte Cell Lines.

BACKGROUND: S-methylmethionine sulfonium chloride was originally called vitamin U because of its inhibition of ulceration in the digestive system. Vitamin U is ubiquitously expressed in the tissues of flowering plants, and while there have been reports on its hypolipidemic effect, its precise function remains unknown. OBJECTIVE: This study was designed to evaluate the anti-obesity effect of vitamin U in 3T3-L1 pre-adipocyte cell lines. METHODS: We cultured the pre-adipocyte cell line 3T3L1 to overconfluency and then added fat differentiation-inducing media (dexamethasone, IBMX [isobutylmethylxanthine], insulin, indomethacin) and different concentrations (10, 50, 70, 90, 100 mM) of vitamin U. Then, we evaluated changes in the levels of triglycerides (TGs), glycerol-3-phosphate dehydrogenase (G3PDH), AMP-activated protein kinase (AMPK), adipocyte-specific markers (peroxisome proliferator-activated receptor γ [PPAR-γ], CCAAT/enhancer-binding protein α [C/EBP-α], adipocyte differentiation and determination factor 1 [ADD-1], adipsin, fatty acid synthase, lipoprotein lipase) and apoptosis-related signals (Bcl-2, Bax). RESULTS: There was a gradual decrease in the level of TGs, C/EBP-α, PPAR-γ, adipsin, ADD-1 and GPDH activity with increasing concentrations of vitamin U. In contrast, we observed a significant increase in AMPK activity with increasing levels of vitamin U. The decrease in bcl-2 and increase in Bax observed with increasing concentrations of vitamin U in the media were not statistically significant. CONCLUSION: This study suggests that vitamin U inhibits adipocyte differentiation via down-regulation of adipogenic factors and up-regulation of AMPK activity.