ISSN:
1420-908X
Keywords:
Key words: Non-steroidal anti-inflammatory drugs (NSAIDs) – Meloxicam – COX-2 inhibitors – Gastric injury – Oxygen radical
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. Aim and Design: In addition to a deficiency of endogenous prostaglandins due to inhibition of cyclo-oxygenase and a host of prostaglandin-mediated effects on mucosal protection, it has recently been proposed that neutrophil- and oxygen radical - dependent microvascular injuries may be important prime events that lead to mucosal injury induced by non-steroidal anti-inflammatory drugs. Therefore, we evaluated the role of oxygen free radicals in the pathogenesis 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 weight).¶Methods: Determinations were made of gastric mucosal injury, xanthine-oxidase, myeloperoxidase and superoxide dismutase activities, as well as the effect of meloxicam on gastric prostaglandin synthesis (PGE2 levels) and glutathione homeostasis.¶Results: Oral administration of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage erosions. The total area of gastric lesions increased with time until 24 hours after dosing. Xanthine-oxidase activity increased significantly after administration of the drug. Myeloperoxidase activity, as an index of neutrophil infiltration, as well as glutathione peroxidase, an important enzyme that scavenges lipid peroxides, were unaffected by meloxicam administration. In addition, superoxide dismutase activity, PGE2 and glutathione levels were significantly reduced.¶Conclusion: These results support the hypothesis that in addition to suppresion of prostaglandin synthesis, oxygen free radicals, probably derived via the action of xanthine oxidase, the decrease in superoxide dismutase activity, and the depletion of mucosal glutathione contribute to the pathogenesis of meloxicam-induced ulceration.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00000217
Permalink
