Protective effect of rebamipide against ammonia-induced gastric mucosal lesions

We investigated the protective effect of rebamipide against ammonia-induced gastric mucosal lesions. Participation of prostaglandin E2 and nitric oxide in the action of rebamipide was also examined. Rebamipide was administered intraperitoneally (10-100 mg/kg) to male Wistar/ST rats (150-325 g) fasted for 24 hr. Thirty minutes later, 1% NH4OH (1 ml) solution was given intragastrically. One hour later, the length of the mucosal lesions was measured (lesion index), and prostaglandin E2 (PGE2) was determined by radioimmunoassay. A 1% NH4OH solution caused gastric mucosal lesions with hemorrhagic necrosis and submucosal edema. PGE2 synthesis was not affected by NH4OH but was significantly increased by rebamipide. Rebamipide decreased the severity of NH4OH-induced gastric mucosal lesions in a dose-dependent manner. Pretreatment with indomethacin (5 mg/kg, subcutaneously) did not affect the protective effect of rebamipide; however, pretreatment with N(omega)-nitro-L-arginine (L-NNA, 1-10 mg/kg, intravenously), an inhibitor of nitric oxide synthase, attenuated the protective effect of rebamipide in a dose-dependent manner. Simultaneous administration of L-arginine (100 mg/kg) and L-NNA completely restored the protective effect of rebamipide, whereas D-arginine was inactive. These results suggest that nitric oxide contributes significantly to the protective effect of rebamipide against ammonia-induced gastric mucosal lesions.