Abstract
Using non-steroidal anti-inflammatory drugs as over-the-counter pain-killers may predispose to gastric ulcer as a side effect. The objective of this study is to investigate the possible benefit of a common statin used in hyperlipedemic patients; atorvastatin (AtoR), in ameliorating the ulcerogenic effect of indomethacin (IndoM), and to explore the possible mechanisms involved. AtoR (10 mg/kg/day) was administered orally for 7 days. At day 7, gastric ulcer was induced by a single dose of IndoM (40 mg/kg i.p.), with or without AtoR pre-treatment. IndoM induced gastric ulcer as evident by notable gastric ulceration in histopathological sections compared to normal control. Gastric tissue in rats receiving IndoM showed significantly higher oxidative stress markers as lipid peroxidation represented by increased malondialdehyde (MDA) content, with significant decrease in gastric tissue nitric oxide (NO) and prostaglandin E2 (PGE(2)) levels, as well as reduction in catalase and superoxide dismutase antioxidant enzymatic activities. In addition, IndoM induced inflammatory signs as shown by the significant increase in tumor necrosis factor-alpha (TNF-alpha) level assessed via ELISA. Pre-administration of AtoR significantly decreased ulcer index (16 +/- 1) compared to that of IndoM alone (34 +/- 2). In addition, AtoR restored normal gastric histological structure and reverted oxidative and inflammatory markers tested. AtoR confers gastro-protection against IndoM-induced ulceration via reducing gastric oxidative stress and increasing gastric NO and PGE2 levels, as well as decreasing the inflammatory marker; TNF-alpha.