Effect of corticosteroids on indomethacin-induced intestinal ulceration in the rat.
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.
D000284:Administration, Oral; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage*; D006854:Hydrocortisone / Q000008:administration & dosage*; D007410:Intestinal Diseases / Q000139:chemically induced / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D010248:Paramethasone / Q000008:administration & dosage*; D011239:Prednisolone / Q000008:administration & dosage*; D051381:Rats; D013997:Time Factors; D014456:Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D001623:Betamethasone; D011239:Prednisolone; D010248:Paramethasone; D006854:Hydrocortisone