Gastric cytoprotection by ebselen against the injury induced by necrotizing agents in rats

The gastric cytoprotective effect of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a novel seleno-organic antioxidative agent, against the insults of necrotizing agents was investigated in rats. Either 0.6 N HCl or acidified ethanol (60% ethanol in 150 mmol/l HCl), given orally in a volume of 1 ml, produced linear hemorrhagic necroses in the gastric mucosa within 1 h. Pretreatment with ebselen at oral doses from 10 to 100 mg/kg significantly inhibited such lesion formation induced by either necrotizing agent in a dose-related manner, and the inhibition at the highest dose (100 mg/kg p.o.) was practically complete. Light microscopic analysis also confirmed that ebselen effectively prevented the formation of deep mucosal necrosis in response to the necrotizing agents. In addition, the protection by ebselen of gastric necrosis induced by either damaging agent was not affected by pretreatment of animals with indomethacin (5 mg/kg s.c.), indicating that the protective effect of this agent was not mediated by the mild irritation on the gastric mucosa. These results demonstrate that ebselen is a potent cytoprotective agent effectively preventing the gastric mucosal injury induced by necrotizing agents.