Protective effect of rebamipide against hydrogen peroxide-induced hemorrhagic mucosal lesions in rat stomach

Intragastric administration of 6% H2O2 induces gastric mucosal hemorrhagic lesions in rats. Intraperitoneal administration of rebamipide at 10 to 100 mg/kg dose-dependently prevented the H2O2-induced mucosal lesions. The fact that cimetidine, ranitidine and omeprazole could not prevent the gastric mucosa from developing H2O2-induced lesions indicates that acid secretion might not be the main cause of these lesions. The protective effect of rebamipide was partially reduced by indomethacin and completely blocked by diethyl maleate, a glutathione depressor. Gastric mucosal glutathione level and glutathione peroxidase and superoxide dismutase (SOD) activities were significantly decreased by 6% H2O2 instillation. Rebamipide at 100 mg/kg significantly inhibited the decreases in gastric mucosal glutathione level and SOD activity. These results suggest that H2O2-induced gastric mucosal lesions might partially involve a decrease in defense activities against reactive oxygen species and that the protective effect of rebamipide might be related to its ability to improve oxidative stress in gastric mucosa.