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

AZZA A.K. EL-SHEIKH MOHAMED A. EL-MOSELHY

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 (PGE2) 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-α) 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-α.


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