Effect of centrophenoxine on water-immersion restraint stress- and chemically-induced gastric ulcers in rats.

Recent studies clearly suggest a role of central nervous system in regulation of gastrointestinal function and defense against ulcerogens. In the present study, attempt was made to investigate the effect of centrophenoxine (CPH), a nootropic drug on gastric acid secretion and experimentally induced gastric ulcer in rats. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with CPH (10-100 mg/kg, i.p.). The effect of orally administered CPH on water-immersion restraint (WIR) stress, indomethacin and ethanol-induced gastric ulcers was also examined. The level of myeloperoxidase (MPO), non-protein sulfhydryls (NP-SH) and gastric wall mucus was measured in the glandular stomach of rats following ethanol-induced gastric lesions. There was a dose-dependent inhibition of gastric acid secretion in the CPH treated rats. Pretreatment with CPH significantly protected gastric mucosa against ethanol and indomethacin induced gastric lesion. Only low dose of CPH (30 mg/kg) was found to be effective against stress ulcers. A significant attenuation of ethanol-induced increase in gastric MPO activity, depletion of NP-SH and reduction of gastric wall mucus was also observed in CPH treated rats. These findings clearly suggest the involvement of endogenous pro-inflammatory mediators and oxidative stress in mediating the gastroprotective effect of CPH.