Effects of meloxicam on oxygen radical generation in rat gastric mucosa

Aim and Design. In addition to a deficiency of endogenous prostaglandins du e to inhibition of cyclo-oxygenase and a host of prostaglandin-mediated eff ects on mucosal protection, it has recently been proposed that neutrophil- oxygen radical - dependent microvascular injuries may be important prime ev ents that lead to mucosal injury induced by non-steroidal anti-inflammatory drugs. Therefore, we evaluated the role of oxygen free radicals in the pat hogenesis of acute gastric ulceration induced by meloxicam, a preferential COX-2 inhibitor. Material: Studies were performed in Wistar rats. Treatment: Meloxicam was given by oral administration (3.75-30 mg/kg body w eight). Methods: Determinations were made of gastric mucosal injury, xanthine-oxida se, myeloperoxidase and superoxide dismutase activities, as well as the eff ect of meloxicam on gastric prostaglandin synthesis (PGE, levels) and gluta thione homeostasis. Results: Oral administration of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage erosions. The total area of gastric lesion s increased with time until 24 hours after dosing. Xanthine-oxidase activit y increased significantly after administration of the drug. Myeloperoxidase activity, as an index of neutrophil infiltration, as well as glutathione p eroxidase, an important enzyme that scavenges lipid peroxides, were unaffec ted by meloxicam administration. In addition, superoxide dismutase activity , PGE(2) and glutathione levels were significantly reduced. Conclusion. These results support the hypothesis that in addition to suppre sion of prostaglandin synthesis, oxygen free radicals, probably derived via the action of xanthine oxidase, the decrease in superoxide dismutase activ ity, and the depletion of mucosal glutathione contribute to the pathogenesi s of meloxicam-induced ulceration.