Effect and mechanism of sucralfate on healing of acetic acid-induced gastric ulcers in rats.

We examined the effect of sucralfate on spontaneous and delayed healing of experimental gastric ulcers and the underlying mechanism of action. Gastric ulcers were produced 5 days after submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of rat stomachs. To delay the healing of ulcers, indomethacin was administered s.c. at 1 mg/kg once daily for 4 weeks from 5 days after the acid injection. Sucralfate, administered p.o. three times daily, significantly accelerated the spontaneous healing of ulcers, the healing rates being 13.7%, 43.7% and 47.1% with 100 mg/kg, 300 mg/kg and 600 mg/kg, respectively. In addition, the drug also significantly prevented the delay in ulcer healing caused by indomethacin, the preventive rates being 56.6% and 83.9% with 300 mg/kg and 600 mg/kg, respectively. Sucralfate, even at 1000 mg/kg, had no effect on the mucosal prostaglandin E2 (PGE2) level around the ulcers and did not affect the reduced PGE2 content caused by indomethacin. A single dose of sucralfate significantly increased the volume and the pH of the gastric contents in a dose-dependent manner, the effects persisting for up to 8 hr. These results suggest that the mechanism by which sucralfate accelerates the healing of gastric ulcers is unrelated to endogenous PGs but related to the acid-neutralizing activity.