Role of gastric mucosal eicosanoid production in the cytoprotection induced by nitecapone.

Nitecapone (3-100 mg/kg orally) dose-dependently (40-97%) decreased the macroscopic gastric lesions induced by ethanol, NaOH, or HCl in the rat. The duration of protection was long, being still 70% at 6 h after dosing. Nitecapone (10-100 mg/kg orally) induced at 1 h after dosing a significant and dose-dependent increase in gastric mucosal prostaglandin E2 release. After the dose of 30 mg/kg the release was sixfold at 2 h and threefold at 12 h. Colloidal bismuth subcitrate (30 mg/kg) stimulated the prostaglandin E2 release only transiently, and sucralfate (400 mg/kg) showed only a tendency to stimulate the release. Indomethacin prevented the nitecapone-induced stimulation of prostaglandin E2 but was unable to counteract the cytoprotective activity of the compound. Nitecapone (30 mg/kg) also caused transient increase (twofold) in the release of 6-keto-prostaglandin F1 alpha and thromboxane B2 and a decrease in both basal and ethanol-induced release of leukotriene C4.