Gastroprotective effect of simvastatin against experimentally induced gastric ulcers in rats: Role of ATP-sensitive K channels

Simvastatin appeared to have additional benefits beyond their lipid lowering effects, which has led to interest in the use of this class of drugs outside the field of cardiovascular disease. Aim: This study aimed to investigate the possible gastroprotective effect of simvastatin against both indomethacin and cold restraint stress (CRS) induced gastric ulcers in rats and to study its effect on gastric mucosal malonaldehyde (MDA) ,nitric oxide (NO)and prostaglandin E2( PGE2) levels in both ulcer models. Exploration of the possible contribution of ATPsensitive K channels in this action. Design: 72 healthy, adult male albino rats were used. The rats were randomly assigned to vehicle (distilled water or carboxymethylcellulose (0.5%), simvastatin, simvastatin +glibenclamide (ATP-sensitive K channels blocker), pretreated groups for 7 days then ulcers were induced using oral indomethacin or cold restraint stress. Assessment of gastric lesions was done, gastric juice parameters ( total acid output, pepsin activity and mucin content ) were determined for each group using pyloric ligation method .Rats from simvastatin pretreated groups in both ulcer models were used for determination of gastric mucosal level of MDA (as indicator of lipid peroxidation) , nitrite (as indicator of NO) and PGE2 levels. Results: Simvastatin displayed significant (P< 0.05) protection against gastric lesions induced by either indomethacin or exposure to cold restraint stress by correction of both ulcer score and the measured gastric juice parameters. This effect was partially blocked by coadministration of glibenclamide. Simvastatin significantly (P< 0.05) reduced gastric mucosal MDA; significantly (P< 0.05) increased in PGE2 levels and corrected nitrite to near normal levels in both ulcer models. Conclusion: This study confirmed the gastroprotective effect of simvastatin in indomethacin induced ulcer in rats and proved it in CRS induced ulcer .The gastroprotective effect of simvastatin is mediated through opening of ATP sensitive K channels, free radical scavenging, increase in gastric mucosal PGE2 and normalization of gastric mucosal NO in both ulcer models. [Dalia M. Abd El Motteleb, Mai M. Hasan . Gastroprotective effect of simvastatin against experimentally induced gastric ulcers in rats: Role of ATP-sensitive K channels. Journal of American Science 2011;7(7):760768]. (ISSN: 1545-1003). http://www.americanscience.org.