Gastro-Protection of Atorvastatin in Indomethacin-Induced Ulcer: Role of Tumor Necrosis Factor-Alpha and Prostaglandins


Affiliations

  • Minia University, Department of Pharmacology, Egypt
  • Sina National College for Medical Studies, Department of Pharmacology and Toxicology, Jeddah, Saudi Arabia

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) a nd 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 - α) level a ssessed 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 PGE 2 levels, as well as decreasing the inflammatory marker; TNF - α.

Keywords

Atorvastatin, Indomethacin, Gastric Ulcer, ProstaglandinE 2 , TNF - α.

Subject Discipline

Pharmacy and Pharmacology

Full Text:

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