Protective effect of Irsogladine on monochloramine induced gastric mucosal lesions in rats:a comparative study with...

AIM:To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH(2)Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective a ctivity.METHODS AND RESULTS:Oral administration of NH(2)Cl-(120mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs.Both irsogladine (1mg/kg-10mg/ kg,po) and rebamipide (30mg/kg-100mg/kg, po) dose dependently prevented the development of these lesions in response to NH(2)Cl, the effect of irsogladine was significant at 3mg/kg or greater, and that of rebamipide only at 100mg/kg. The protective effect of irsogladine on NH(2)Cl induced gastric lesions was significantly reduced by N( G) nitro L arginine methyl ester (L-NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L-NAME. Topical application of NH(2)Cl-(20mM)caused a marked reduction of potential difference (PD) in exvivo stomachs. This PD reduction was not affected by mucosal application of irso-gladine, but significantly prevented by rebamipide. The mucosal exposure to NH(4)OH (120mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH(4)OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L-NAME sensitive manner.CONCLUSION:These results suggest that (1)NH(2)Cl gen-erated either exogenously or endogenously damages the gastric mucosa, (2)both irsogladine and rebamipide protect the stomach against injury caused by NH(2)Cl,and (3)the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.