[Show abstract][Hide abstract] ABSTRACT: Earlier studies have suggested an important role of glutathione (GSH) in cytoprotection against free radicals induced oxidative damage. This study reports gastroprotective effects of a cysteine precursor, L-2-oxothiazolidine-4-carboxylate (OTC), in experimental models of gastric secretion and ulceration. Acid secretion studies (volume and acidity) were undertaken in pylorus-ligated rats whereas the gastric lesions were induced by ethanol. Different groups of animals were treated with OTC (0, 100, 200 and 400 mg/kg). The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and myeloperoxidase (MPO) were measured in the glandular stomach of rats following ethanol-induced gastric lesions. Both medium and high doses of OTC significantly reduced the volume and acidity of gastric secretion in pylorus-ligated rats. Pretreatment with OTC significantly and dose-dependently attenuated the formation of ethanol-induced gastric lesion. OTC significantly protected the gastric mucosa against ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. The gastroprotective effects of OTC may be attributed to its ability to inhibit neutrophils activity and replenish GSH demand.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 03/2012; 64(3):233-7. · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Earlier studies have implicated reactive oxygen species and transitional metals in the pathogenesis of gastric lesions. In this study, we have evaluated the effect of 2,3-dimercaptopropanol (DMP), a thiol compound and metal chelator, on chemically induced gastroduodenal ulcers in rats. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with DMP (3-100 mg/kg, i.p.). The effect of orally administered DMP on cysteamine-induced duodenal ulcers and ethanol-induced gastric ulcers was also tested. The level of nonprotein sulfhydryls (NP-SH) and gastric wall mucus was measured in the glandular stomach of rats treated with ethanol. None of the dose of DMP affected the volume or acidity of gastric secretion. Low doses of DMP (3 and 10 mg/kg) significantly reduced cysteamine-induced duodenal ulcers, whereas the high doses (30 and 100 mg/kg) were ineffective in this model. All the doses of DMP significantly and dose dependently attenuated ethanol-induced gastric lesions. The adverse effects of ethanol on gastric wall mucus and NP-SH were significantly and dose dependently reversed by DMP. In conclusion, the protective effects of DMP appear to be independent of gastric acid secretion and may be associated with counteracting the oxidative stress by replenishing glutathione and reducing the pool of transition metals.
Fundamental and Clinical Pharmacology 04/2011; 26(3):402-9. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, statins have appeared to have additional benefits beyond their lipid lowering effects, which has led to the interest in the use of this class of drugs outside the realm of cardiovascular disease. Simvastatin (SIM) is a commonly prescribed statin with anti-inflammatory and antioxidant properties. Excessive generation of oxygen-derived free radicals (ODFR) and proinflammatory mediators has been implicated in the pathogenesis of gastric ulcers. This investigation aimed to study the effect of SIM on experimentally induced gastric acid secretion and ulcer formation.
Adult Wistar rats were divided into experimental groups containing six animals. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with SIM (20, 40, and 60 mg/kg). The effect of orally administered SIM was also studied on indomethacin- and ethanol-induced gastric ulcers. The levels of myeloperoxidase (MPO), non-protein sulfhydryls (NP-SH), nitric oxide (NO), antioxidant enzymes, and gastric wall mucus were measured in the glandular stomach of rats following ethanol-induced gastric lesions.
Administration of SIM significantly and dose-dependently inhibited the volume of gastric secretion and the acidity. Pretreatment with SIM significantly reduced the formation of indomethacin- and ethanol-induced gastric lesions. The antiulcer activity of SIM was associated with significant attenuation of adverse effects of ethanol on gastric wall mucus, NP-SH and MPO. SIM modified the gastric NO levels and reversed the ethanol-induced decrease in glutathione-S-transferase and increase in superoxide dismutase and catalase.
These findings clearly suggest the involvement of proinflammatory agents and ODFR in the pathogenesis of gastric lesions. The gastroprotective effects of SIM are mediated by inhibition of neutrophils activity, reduction of oxidative stress, and maintenance of vascular integrity. This study was conducted in rats; its relevance to human gastric ulcers is not known and warrants further study.
Journal of Gastroenterology and Hepatology 01/2008; 22(12):2316-23. · 3.63 Impact Factor