Effects of food intake and oxidative stress on intestinal lesions caused by meloxicam and piroxicam in rats

Large intestinal ulcers, bleeding and perforation are occasionally due to n on-steroidal anti-inflammatory drugs (NSAID). In addition to suppression of prostaglandins, synthesis, a number of factors have been implicated, inclu ding enterohepatic recirculation, food intake and vascular injury with oxyg en free-radical generation. The present study aimed to determine the effect of food intake and the role of oxidative stress in the pathogenesis of int estinal injury induced by oral administration of meloxicam (preferential cy clooxygenase-2 inhibitor) vs, piroxicam (preferential cyclooxygenase-1 inhi bitor). Therefore, the activity of oxidative stress-related enzymes such as myeloperoxidase, xanthine oxidase and superoxide dismutase, as well as lev els of lipid peroxides and glutathione homeostasis were studied in an exper imental model using re-fed rats. The animals treated with piroxicam (10-20 mg/kg) had a dose-dependent increase in the severity of intestinal lesions, but only the highest dose of meloxicam (15 mg/kg) caused macroscopic damag e. The severity of piroxicam and meloxicam-induced damage was correlated wi th a significant increase of xantine oxidase activity and a decrease of sup eroxide dismutase activity and glutathione levels (P < 0.05 and P < 0.001 v s, control). In contrast, there was no significant neutrophil infiltration of the intestine after dosing. Our results support the hypothesis that oxyg en free radicals, probably derived via the action of xantine oxidase, the d ecrease in superoxide dismutase activity, and depletion of mucosal glutathi one contribute to the pathogenesis of meloxicam and piroxicam-induced intes tinal ulceration in re-fed rats. (C) 2001 Elsevier Science B.V. All rights reserved.