Healing process of duodenal ulcers induced by indomethacin plus histamine in rats

Healing of duodenal ulcers induced by indomethacin + histamine was investigated in rats. Animals were treated with indomethacin (5 mg/kg, s.c., once daily) and histamine (40 mg/kg, s.c., 3 times every 2.5 h after indomethacin treatment) for 2 days under fasting conditions, and they were fed normally thereafter. The duodenal ulcers so induced were confined to the proximal part of the duodenum and penetrated to the muscular mucosa with an incidence of over 80% when determined 32 h after the first injection of indomethacin (day 1). The ulcers became smaller and shallower within 7 days with granulation from the ulcer base, the mucosa grew in from the edges over the surface of granulation tissue, and they had healed almost completely after 15 days with epithelial regeneration from the edge of the ulcers. The healing of ulcers was significantly promoted by a 5-day treatment with an antacid (Al(OH)3) as well as antisecretory agents (omeprazole, cimetidine, propantheline bromide) and 16,16-dimethyl prostaglandin E2 at the dose which produced a potent inhibition of acid output and a marked increase in duodenal alkaline secretion. These results suggest that the duodenal ulcers induced in rats by indomethacin + histamine may provide a useful model for studying the healing process of duodenal ulcers and for the evaluation of the drugs with possible effects on ulcer healing.