Ameliorative Effects of Sitagliptin against Indomethacin-Induced Gastric Ulcer in Rats

Abstract

The present study investigated the potential protective effect of sitagliptin against indomethacin-induced gastric ulcer in rats. Sitagliptin was administered in two doses (5 and 10 mg/kg/day, p.o.) for 14 days, then gastric ulcer was induced by a single dose of indomethacin (50 mg/kg, p.o.). In another set of experiments, the effects of sitagliptin on gastric secretion were tested in pylorus-ligated rats. Sitagliptin significantly decreased the ulcer index, malondialdehyde, tumor necrosis factor-α, and cleaved caspase-3, and significantly increased the reduced glutathione, superoxide dismutase and prostaglandin E₂ in gastric mucosa of indomethacin-challenged rats. Sitagliptin also reduced the volume of gastric secretion, total acid concentration, and pepsin activity in pylorus-ligated rats. Histopathological examination showed that sitagliptin markedly minimized the gastric mucosal injuries caused by indomethacin. Both sitagliptin doses significantly protected against indomethacin-induced gastric lesions in rats, most probably by inhibiting oxidative stress, inflammation, and apoptosis.