Protective effects of zinc in indomethacin-induced gastric mucosal injury:evidence for a dual mechanism involving lipid peroxidation and nitric oxide

Background: Indomethacin causes gastric mucosal injury, although the pathog enesis is not fully understood, Zinc, is known to have gastroprotective eff ects in both humans and experimental animals. Aim: To determine (i) the protective effects of zinc in indomethacin-induce d gastric mucosal injury in rats, and (ii) whether these cytoprotective eff ects are mediated by changes in gastric lipid peroxidation and/or nitric ox ide synthase activity, Methods: Gastric lesions were induced in rats by the intragastric administr ation of indomethacin. Morphological changes, lipid peroxidation (malondial dehyde levels) and nitric oxide synthase activity were determined in animal s pre-treated with zinc sulphate and in controls, Results: Indomethacin significantly increased malondialdehyde levels and de creased NOS activity. These effects were attenuated by pre-treatment with z inc (P < 0.005 and 0.0001, respectively), The protective effects of zinc we re readily abolished in animals pretreated with N-nitro-L-arginine methyl e ster (L-NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre-treatment, Conclusions: Zinc provides protection against indomethacin-induced gastric mucosal injury. These protective effects result from the inhibition of lipi d peroxidation and the preservation of mucosal nitric oxide synthase.