PROTECTIVE EFFECT OF REBAMIPIDE AGAINST AMMONIA-INDUCED GASTRIC-MUCOSAL LESIONS

We investigated the protective effect of rebamipide against ammonia-in duced gastric mucosal lesions. Participation of prostaglandin E-2 and nitric oxide in the action of rebamipide was also examined. Rebamipide was administered intraperitoneally (10-100 mg/kg) to male Wistar/ST r ats (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 E- 2 (PGE(2)) was determined by radioimmunoassay. A 1% NH4OH solution cau sed gastric mucosal lesions with hemorrhagic necrosis and submucosal e dema. PGE, synthesis was not affected by NH4OH but was significantly i ncreased by rebamipide. Rebamipide decreased the severity of NH4OH-ind uced gastric mucosal lesions in a dose-dependent manner. Pretreatment with indomethacin (5 mg/kg, subcutaneously) did not affect the protect ive effect of rebamipide; however, pretreatment with N-omega-nitro-L-a rginine (L-NNA, 1-10 mg/kg, intravenously), an inhibitor of nitric oxi de 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, w hereas D-arginine was inactive. These results suggest that nitric oxid e contributes significantly to the protective effect of rebamipide aga inst ammonia-induced gastric mucosal lesions.