Effect of Atorvastatin on Indomethacin-Induced Gastric Ulceration in Rats: Role of Nitric Oxide and Gastric Motility

Abstract Background: Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulceration caused by inhibition of prostaglandins. Atorvastatin, a widely used hypolipidemic agent, has many beneficial pleiotropic effects like anti-inflammatory and antioxidant actions, it may also inhibit smooth muscle contraction. Objectives: The present study was to examine the gastric effect of atorvastatin in rats pretreated with indomethacin. Materials and Methods: Forty-five male albino rats were divided into seven groups. Group 1 (control): solvent, 10% hydroxy propyl cyclodextrin/10% of tween 80 (5 days), last day saline. Group 2: solvent (5 days), last day indomethacin. Group 3: simvastatin 20 mg/kg (5 days), last day saline. Group 4: atorvastatin 20 mg/kg (5 days), last day saline. Group 5: simvastatin 20 mg/kg (5 days), last day indomethacin. Group 6: atorvastatin 20 mg/kg (5 days), last day indomethacin. Group 7: atorvastatin 40 mg/kg (5 days), last day indomethacin. Serum nitric oxide (NO) was measured using a commercial kit. Serum malondialdehyde (MDA) was read by a spectrophotometer at 532 nm. Gastric muscle contractility was studied with an isolated tissue bath. Results: Indomethacin-induced gastric ulceration with increased MDA, decreased NO, and enhanced gastric motility. By contrast, atorvastatin dose-dependently reduced indomethacin ulceration enhanced NO, and decreased MDA level with inhibition of gastric motility. Conclusion: Atorvastatin inhibits indomethacin-induced gastric ulceration by enhancing NO level and secondary to inhibition of gastric motility.