GASTRO-PROTECTION OF ATORVASTATIN IN INDOMETHACIN-INDUCED ULCER: ROLE OF TUMOR NECROSIS FACTOR-ALPHA AND PROSTAGLANDINS

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 mechanismsinvolved. AtoR (10 mg/kg/day) was administered orally for 7 days. At day 7, gastric ulcer was induced by a single dose ofIndoM (40 mg/kg i.p.), with or without AtoR pre-treatment. IndoM induced gastric ulcer as evident by notable gastriculceration in histopathological sections compared to normal control. Gastric tissue in rats receiving IndoM showedsignificantly 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 (PGE2) levels, as well as reductionin catalase and superoxide dismutase antioxidant enzymatic activities. In addition, IndoM induced inflammatory signs asshown by the significant increase in tumor necrosis factor-alpha (TNF-α) level assessed via ELISA. Pre-administration ofAtoR significantly decreased ulcer index (16±1) compared to that of IndoM alone (34±2). In addition, AtoR restored normalgastric histological structure and reverted oxidative and inflammatory markers tested. AtoR confers gastro-protection againstIndoM-induced ulceration via reducing gastric oxidative stress and increasing gastric NO and PGE2 levels, as well asdecreasing the inflammatory marker; TNF-α