Effect of corticosteroids on indomethacin-induced intestinal ulceration in the rat

Abstract

A single dose of indomethacin induces a severe gastrointestinal syndrome in the rat, characterized by intestinal ulceration, perforation, and death. The mechanism by which indomethacin induces this syndrome is unclear, although it has been suggested that a loss of mucosal integrity leads to inflammation and necrosis of the intestinal wall. The purpose of the present investigation was to study the effect of corticosteroids on indomethacin-induced ulceration. Prednisolone administered orally, even as a single dose (10 mg/rat), significantly reduced the severity of ulceration following indomethacin. This protective effect was most pronounced when prednisolone was administered 1 hr postindomethacin and decreased as the period between indomethacin and prednisolone administration increased. Of the steroids studied, the rank order of efficacy in reducing the severity of indomethacin-induced ulceration was paramethasone acetate > betamethasone > prednisolone. Hydrocrotisone was not significantly effective at the doses ultilized. Our results suggest that corticosteroids exert a cytoprotective effect on intestinal mucosa similar to that produced by prostaglandins.