Role of prostanoids in the protective actions of BW755C on the gastric mucosa

Abstract

The ability of BW755C to reduce ethanol- or indomethacin-induced gastric damage and the role of prostanoids in the mechanism of this action were examined in the rat. BW755C (1-100 mg/kg) caused a dose-related reduction in the amount of damage produced by oral administration of 40% ethanol in 100 mM HCl. At the doses tested, BW755C had no significant effect on mucosal 6-keto-prostaglandin F1 alpha synthesis, but did cause a dose-dependent reduction in thromboxane B2 synthesis. The effect on thromboxane synthesis may be due to a selective inhibition of platelet cyclo-oxygenase by BW755C. The higher doses of BW755C (50 and 100 mg/kg) caused a significant increase in the volume of fluid present in the gastric lumen, which may contribute to the protective action of the drug against ethanol-induced damage. Oral administration of BW755C (50 mg/kg) significantly reduced the extent of gastric damage caused by subcutaneous injection of indomethacin (20 mg/kg) indicating that it is unlikely that the protective action of BW755C is mediated by endogenous prostanoids. The mechanism of the protective actions of BW755C may be related to its reported ability to inhibit lipoxygenase or to its actions as a free-radical scavenger.