Mepirizole-induced duodenal ulcers in rats and their pathogenesis

Duodenal ulcers were produced in rats following either an oral or parenteral administration of 200 mg/kg of mepirizole, a nonsteroidal antiinflammatory agent. Deep ulcers, including perforated ones, were induced in the proximal duodenum with an incidence of over 90%. Mortality due to perforation was less than 5%. The agent also induced several erosions in the antrum. Feeding of animals after the ingestion of mepirizole markedly suppressed the development of both duodenal ulcers and gastric erosions. Antacids, anticholinergic agents, a histamine H2-receptor antagonist and 16-DMPGE2 dose-dependently inhibited mepirizole-induced duodenal ulcers. Gastric erosions were also significantly inhibited by antacids and anticholinergic agents but not by a histamine H2-receptor antagonist and 16-DMPGE2. Intraduodenally administered mepirizole dose-dependently inhibited the gastric secretion in pylorus-ligated rats. This ulcer model should be useful for screening antiulcer agents and for the study of pathogenesis of duodenal ulcers and gastric erosions.