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.