Indomethacin-induced gastric antral ulcers in hamsters.
Antral ulcers account for about half of gastric ulcers in humans. An animal model was developed to produce such ulcers. Indomethacin given subcutaneously to normally fed hamsters produced antral ulcers within 1-5 h, dose dependently. These ulcers penetrated the muscularis mucosae. With repeated administration of indomethacin and longer duration of treatment, the lesions became more severe and most animals died with perforated antral ulcers after 2-5 days. Like indomethacin, aspirin given orally also produced antral ulcers in hamsters. Indomethacin reduced the formation of prostaglandin E2, prostaglandin F2 alpha, and 6-keto prostaglandin F1 alpha by the antral mucosa, and increased gastric acid output more than twofold. The ulcers were prevented by various antisecretory agents (cimetidine, methscopolamine bromide, and omeprazole), and the antiulcer dose of each of these agents corresponded to the antisecretory dose. By contrast, several prostaglandins prevented the ulcers at very low, nonantisecretory doses. 16,16-Dimethyl prostaglandin E2 prevented the ulcers at a dose nearly 3000 times lower than the gastric antisecretory ED50. The mechanism by which prostaglandins prevent formation of these ulcers is unknown, but the effect is consistent with cytoprotection, i.e., protection of the gastric mucosa by nonantisecretory doses. Indomethacin-induced antral ulcers appear to depend on two factors: a depletion of prostaglandin content of the antrum and gastric hyperacidity.
Kolbasa
K P
KP
Diabetes and Gastrointestinal Research, Upjohn Company, Kalamazoo, Michigan.
Lancaster
C
C
Olafsson
A S
AS
Gilbertson
S K
SK
Robert
A
A
D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006224:Cricetinae; D015232:Dinoprostone; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D008297:Male; D008647:Mesocricetus; D009853:Omeprazole / Q000627:therapeutic use; D010439:Peptic Ulcer Perforation / Q000517:prevention & control; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced*; D013997:Time Factors
D011458:Prostaglandins E; D002927:Cimetidine; D015232:Dinoprostone; D009853:Omeprazole; D001241:Aspirin; D007213:Indomethacin