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.

The Photoprotective Effect of S-Methylmethionine Sulfonium in Skin.

S-Methylmethionine sulfonium (SMMS) was reported to have wound-healing effects; we therefore have investigated the photoprotective effect of SMMS in the present study. SMMS increased the viability of keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (hDFs) following ultraviolet B (UVB) irradiation, and reduced the UVB-induced apoptosis in these cells. SMMS increased the phosphorylation of extracellular signal-regulated kinases (ERK), and the inhibitor of the mitogen-activated protein kinase pathway significantly decreased the SMMS-induced viability of KPCs and hDFs. In addition, SMMS attenuated the UVB-induced reactive oxygen species (ROS) generation in KPCs and hDFs. SMMS induced the collagen synthesis and reduced the matrix metalloproteinase-1 expression in UVB-irradiated hDFs. In animal studies, application of 5% and 10% SMMS before and after UVB-irradiation significantly decreased the UVB-induced erythema index and depletion of Langerhans cells. In summary, SMMS protects KPCs and hDFs from UVB irradiation, and reduces UVB-induced skin erythema and immune suppression. Therefore, SMMS can be used as a cosmetic raw material, and protect skin from UVB.

[ABOUT CO-OCCURRENCE OF CRHONIC PANCREATITIS WITH GASTRODUODENAL DISEASES].

The article summarizes clinical features of the course when chronic pancreatitis goes in combination with diseases of gastroduodenal and hepatobiliary systems and features of functional and morphological changes. The article also represents justification of need to include the combined medicine Doktovit (combination of Dexpanthenol and S-methylmethionine) into complex treatment of the pathology, describes mechanism of its gastro protective and reparative action.

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.

Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats.

In this study, we aimed to investigate the effects of vitamin U (Vit U) on valproic acid (VPA)-induced liver damage. Female Sprague Dawley rats were randomly divided into four groups. Group I was intact control animals. Group II was control rats given Vit U (50 mg/kg/day) for fifteen days. Group III was given only VPA (500 mg/kg/day) for fifteen 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 were fasted overnight and then sacrificed under ether anesthesia. Liver tissue was taken from animals, homogenized in 0.9% saline to make up to 10% homogenate. Liver aspartate and alanine transaminases, alkaline phosphatase, lactate dehydrogenase, myeloperoxidase, sorbitol dehydrogenase, glutamate dehydrogenase and xanthine oxidase activities and lipid peroxidation levels were increased and paraoxonase activity and glutathione levels were decreased in VPA group. Treatment with Vit U reversed these effects. These results demonstrated that administration of Vit U is a potentially beneficial agent to reduce the liver damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

Effects of Zn(II) complex with vitamins C and U, and carnitine on metabolic syndrome model rats.

The insulinomimetic activity of a Zn(ii) complex is reported. The effects of the Zn(ii) complex with ascorbic acid (Vitamin C; VC), methylmethionine sulfonium chloride (Vitamin U; VU) and l-carnitine were assessed in diet-induced metabolic syndrome model rats. Zn(VU)(2)Cl(2) and Zn(VC)Cl(2) were suggested to be useful supplementary materials for preventing metabolic syndrome by reducing visceral adipose tissues or accelerating blood fluidity.

Effect of s-methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs.

OBJECTIVE: To assess the value of s-methylmethionine sulphonium chloride (SMMSC) (200 mg/kg) on nutritional performance of pigs and as prevention or therapy for oesophagogastric ulcers. DESIGN: Sixty pigs from a high health status herd with continuing oesophagogastric ulcer problems were endoscopically assessed for the presence or absence of oesophagogastric ulcers. Forty-eight pigs were then selected and allocated according to an initial oesophagogastric epithelial (ulcer score) classification to replicated treatment groups in a 2 x 2 factorial design. Weight gain and feed intake were measured over 49 d, after which pigs were killed and stomachs were collected, re-examined and scored for oesophagogastric ulceration. RESULTS: There was no difference over the 49 d in weight gain, feed intake and backfat in pigs with and without SMMSC supplementation between pigs with or without fully developed oesophagogastric ulcers at the start of the study. In pigs with an initially low ulcer score, feeding SMMSC did not prevent further oesophagogastric ulcer development. No significant effect of SMMSC was apparent when final mean oesophagogastric ulcer scores were compared in pigs with existing high ulcer score. However, further analysis of the changes in individual pig oesophagogastric ulcer scores during the experiment showed that the observed reductions in scores of the high ulcer group was significantly different from all other groups. CONCLUSION: This study has indicated that supplementation of pig diets with SMMSC cannot be justified unless the slight ulcer score improvement observed could be translated to some commercial production advantage such as a reduction in pig mortalities due to oesophagogastric ulcers. This study has further confirmed the benefit of endoscopy as a tool to enable objective assessment of oesophageal gastric health.

[Studying the anti-ulcer activity of gastrobiol].

Gastrobiol--a new preparation comprising a mixture of lyophilized sea-buckthorn oil, vitamin U, and magnesium oxide, produces a pronounced antiulcerous action on the mucous membrane of the stomach and duodenum. The regenerative effect of gastrobiol is more pronounced than that of pure sea-buckthorn oil and methyluracil.

[The effect of cobavit on glutathione system in patients with bleeding gastroduodenal ulcer]. / Vliianie kobavita na sistemu glutationa u bol'nykh s krovotochashchei gastroduodenal'noi iazvoi.

Index of glutathione system studied in 20 healthy persons (KG-1), in 20 with non-complicated duodenal ulcer (KG-2), in 210 patients with bleeding gastroduodenal ulcer, in 77 in early period after different operations. Results obtained showed that ulcer disease, complicated with bleeding was characterized by significant changes in glutathione system degree of which was depended on amount of the blood lost. Operations in early period enhanced disorders in glutathione system. Inclusion of cobavit into the complex of postoperative therapy provided recovery of glutathione pool activation of glutathiontransferase and glutathionreductase reaction that resulted in increase of withdrawal of toxic metabolites and activation of biosynthetic processes in patient's organism.

[The anti-ulcer action of dibunol (Tonarol)]. / Protivoiazvennoe deistvie dibunola (tonarola).

In experimental study of antiulcerative activity of dibunol on various models of gastric ulcers in rats the drug caused a marked antiulcerative effect in all of them, reduced the incidence of ulcer formation, and shortened the time of ulcer healing. In a model of "acetic" ulcer dibunol oil solution led to quick normalization of lipid peroxidation in the gastric mucosa, which was evidence of high antioxidant activity in cases of ulcer lesions.

Effect of hammer mill screen size and addition of fibre or S-methylmethionine-sulphonium chloride to the diet on the occurrence of oesophagogastric lesions in fattening pigs.

Four groups of about 86 pigs from a common source were fed a grower diet from 25 kg to 45 kg liveweight, and then from 45 to 107 kg liveweight they were offered one of four diets ad libitum: A) normal commercial feed, ground through a 3 mm screen (the control diet), B) the same diet ground through a 6 mm screen, C) the control diet to which lucerne meal was added before the diet was ground to increase its crude fibre content, and D) the control diet to which was added 400 ppm S-methylmethionine-sulphonium chloride (MMSC). All the diets were pelleted. Approximately 21 per cent of the animals fed the control diet had severe oesophagogastric erosions and/or ulcers after slaughter. The addition of 400 ppm MMSC decreased (P = 0.066) the proportion of severe oesophagogastric erosions and/or ulcers by about 50 per cent compared with the control diet. The diet with the higher crude fibre content (but finely ground) did not have a significant effect on the proportion of severe oesophagogastric erosions and/or ulcers. There was a tendency for the pigs fed the diet ground through a 6 mm screen instead of a 3 mm screen, to have fewer severe oesophagogastric erosions and/or ulcers. However, there were only small differences between the particle size distribution obtained from the wet sieve analysis of the two diets. As a result, the observed tendency for a decrease in the proportion of severe oesophagogastric erosions and/or ulcers in pigs fed the diet milled through the larger screen size was of questionable significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulfhydryl-containing agents in the treatment of gastric bleeding induced by nonsteroidal anti-inflammatory drugs.

In a double-blind study involving 172 patients, the author investigated the effect of sulfhydryl-containing agents (cysteine and methylmethionine sulfonium chloride [MMSC]) on hematemesis resulting from erosive gastritis induced by nonsteroidal anti-inflammatory drugs. The 56 patients who received cysteine (200 mg orally four times a day) and the 59 patients who received MMSC (500 mg orally four times a day) were significantly (p < 0.01) more hemodynamically stable, with no rebleeding, than the 57 patients who made up a control group. Endoscopy carried out 48 hours after admission demonstrated that gastric erosions were still present in a significantly (p < 0.01) higher number of patients in the control group (20 [35%]) than in patients receiving cysteine (6 [11%]) and in patients receiving MMSC (7 [12%]). Eighteen patients (32%) in the control group required blood transfusion because of continued bleeding or rebleeding compared with only 3 patients (5%) receiving cysteine and 2 patients (3%) receiving MMSC (p < 0.01). Emergency surgery was necessary in 13 patients (23%) in the control group and in 1 patient (2%) in the group receiving cysteine who had rebleeding. Four patients in the control group died postoperatively. The results show that sulfhydryl-containing agents stimulate the healing of erosive gastritis induced by nonsteroidal anti-inflammatory drugs and protect against the complications of bleeding produced by the gastritis.

Protection against chronic gastric ulceration in the rat with sulfhydryl-containing agents.

Reserpine (intraperitoneal, 5 mg/kg every day for 5 days) produced chronic ulceration of the rat stomach 2 weeks postdose. Gavage with 1% DL-cysteine or DL-methionine-S-methylsulfonium chloride at 1 mL/day for 2 weeks and 5 days protected against ulceration in 30% of the rats, and this protection extended to 80% of cases with 2% solutions. Similar gavage with 5% solutions protected all rats against ulceration without significantly influencing the basal H+ output [13.1 +/- 0.3 and 14.2 +/- 0.2 mumol for DL-cysteine and DL-methionine-S-methylsulfonium chloride, respectively, versus 15.1 +/- 0.4 mumol (mean +/- standard error of the mean; n = 10)]; that is, cytoprotection was achieved.

Sulphydryl-containing agents: a new approach to the problem of refractory peptic ulceration.

Refractory peptic ulceration is the term applied to those gastric and duodenal ulcers which remain unhealed despite active treatment for at least 3 months. Sulphydryl-containing agents stimulate the formation of gastrointestinal mucus, bind the oxygen-derived free radicals that mediate tissue damage and play an important role in protein synthesis. This is the first report which suggests that these agents stimulate the healing of refractory gastric and duodenal ulceration without any adverse events.

Role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. A new approach.

This double-blind randomised study investigated the role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. To this end, DL-cysteine (200 mg 4 times daily) and DL-methionine-methyl sulphonium chloride (MMSC, 500 mg 4 times daily) were administered orally. Patients with recurrent attacks of moderate proctosigmoidal ulcerative colitis, despite prophylaxis by oral sulphasalazine (2 g daily), were given prednisolone by mouth, 10 mg four times a day, sulphasalazine by mouth, 500 mg four times a day, and morning and evening retention enema (Predsol 20 mg) alone or with cysteine or MMSC. After 2 weeks of treatment with sulphasalazine and prednisolone, 51% of patients (n = 45) were symptom free. Addition of cysteine (n = 46) or MMSC (n = 47) to this regimen controlled the symptoms within 2 weeks in 85% of patients (p < 0.01). During 12 months of prophylactic treatment, 5% of patients (n = 42) receiving sulphasalazine (2 g daily) and cysteine and 5% of patients (n = 41) taking sulphasalazine (2 g daily) and MMSC relapsed, relative to 27% of cases with sulphasalazine (2 g daily) alone (p < 0.01). These results demonstrate that sulphydryl-containing agents play a key role in the treatment of and protection against ulcerative colitis.

Role of sulfhydryl-containing agents in the healing of erosive gastritis and chronic gastric ulceration in the rat.

One milliliter of 1, 2, or 5% DL-cysteine (cysteine) or DL-methionine methylsulfonium chloride (MMSC) was instilled into the rat stomach 1, 24, and 48 h after giving ethanol (1 mL of 40% solution) by gavage. One hour following the administration of ethanol, gastric mucosal injury was seen in all the animals (22.6 +/- 1.1 mm2, mean +/- SEM; n = 10). Twenty-four hours after giving the ethanol, all the rats treated with cysteine or MMSC still had the mucosal injury. Treatment with 2% cysteine or MMSC significantly (p less than 0.01) reduced the extent of this injury (10.2 +/- 0.6 and 10.1 +/- 0.5 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10), an action that was similarly achieved by the 5% solutions (10.1 +/- 0.5 and 9.9 +/- 0.3 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10). Forty-eight hours following the administration of ethanol, 30% of the animals given 1% cysteine or MMSC still had gastric mucosal injury, which was significantly (p less than 0.001) less extensive than that seen with ethanol alone (3.8 +/- 0.3 and 4.1 +/- 0.3 mm2, respectively, versus 13.1 +/- 0.8 mm2, mean +/- SEM; n = 10). At this time period, however, none of the animals treated with 2 or 5% solutions of cysteine or MMSC still had any injury. Healing of the ethanol-induced injury was confirmed microscopically and was achieved by regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of oxygen-derived free radicals in mechanism of acute and chronic duodenal ulceration in the rat.

This study employed the oxygen-derived free radical removing agents DL-cysteine, methyl-methionine sulfonium bromide (MMSB), dimethyl sulfoxide (DMSO), and allopurinol to examine the role of oxyradicals in the mechanism of acute and chronic duodenal ulceration in the rat. These agents were administered by gavage under light ether anesthesia. All rats infused subcutaneously for 24 hr with pentagastrin (4 micrograms/kg/min) and carbachol (0.8 microgram/kg/min) developed acute duodenal ulceration and hyperchlorhydria (68 +/- 6.1 mumol vs 12.5 +/- 0.3 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol provided dose-dependent protection against this ulceration without significantly influencing the hyperchlorhydria. One percent solutions of these agents protected at least 20% of rats against ulceration. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 70% of rats against ulceration and similar concentrations of allopurinol protected all animals. All rats having intramuscular reserpine (0.1 mg/kg) every day for six weeks developed chronic duodenal ulceration and hyperchlorhydria (52 +/- 3.1 mumol vs 13.1 +/- 0.7 mumol, mean +/- SEM, N = 10, P less than 0.001). Pretreatment with DL-cysteine, MMSB, DMSO, or allopurinol achieved dose-dependent protection against ulceration without significantly influencing the hyperchlorhydria. One percent solutions of DL-cysteine, MMSB, or DMSO protected at least 60% of rats against ulceration; however, a similar concentration of allopurinol protected 80% of animals. Five or 10% solutions of DL-cysteine, MMSB, or DMSO protected at least 80% of rats against ulceration and similar concentrations of allopurinol protected all rats.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anti-ulcer action of the sodium salt of N-(4-sulfolanol-3-yl) methionine]. / Protivoiazvennoe deistvie natrievoi soli N-(4-sul'folanol-3-il) metionina.

Sodium salt of N-(4-solfolanol-3-yl)methionine studied on 13 models of gastric ulcers in rats was shown to have antiulcerative activity both during preventive and therapeutic use as well as the capability to prevent and abolish the ulcerogenic effect of some drugs.