Dulcerozine-induced duodenal ulcers in rats: a simple, highly-reliable model for evaluating anti-ulcer agents

Dulcerozine-induced duodenal ulcers in rats were studied in order to establish the optimum conditions for a routine production of ulcers and to elucidate their possible pathogenesis. Single doses of dulcerozine administered either subcutaneously or orally produced a dose-related duodenal ulceration in rats. The ulcerogenic effect of dulcerozine was most potent when given subcutaneously to 24-hr fasted animals at 300 mg/kg. At this dose, deep or perforating ulcers were consistently produced within 18 hr, but mortality due to general toxicity of the agent was excluded at least up to 48 hr. Feeding of animals resulted in a significant reduction in susceptibility to dulcerozine. An antacid and antisecretory agents prevented dulcerozine-induced duodenal ulceration in a dose-dependent manner. Either pylorus ligation or vagotomy completely inhibited duodenal ulceration in response to dulcerozine. In addition, an ulcerogenic dose (300 mg/kg s.c.) of dulcerozine evoked a sustained gastric hypersecretion in pylorus ligated rats. These results suggest that a stimulating action on gastric secretion may be, at least in part, responsible for the ulcerogenic property of dulcerozine. The present study provides a new reliable model for investigations of the pathogenesis and therapy of duodenal ulcer disease.