Role of Gastric Mucosal Eicosanoid Production in the Cytoprotection Induced by Nitecapone

Abstract

Nitecapone (3–100 mg/kg orally) dose-dependently (40–97%) decreased the macroscopic gastric lesions induced by ethanol, NaOH, or HC1 in the rat. The duration of protection was long, being still 70% at 6h 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 F_1α and thromboxane B₂ and a decrease in both basal and ethanol-induced release of leukotriene C₄.

Key Words:

• Cytoprotection
• ethanol
• gastroprotection
• leukotrienes
• prostaglandins