REBAMIPIDE ATTENUATES INDOMETHACIN-INDUCED GASTRIC-MUCOSAL LESION FORMATION BY INHIBITING ACTIVATION OF LEUKOCYTES IN RATS

Granulocyte elastase released from activated leukocytes plays an impor tant role in leukocyte infiltration. Since activated leukocytes have b een shown to be involved in the pathogenesis of gastric mucosal lesion formation induced by nonsteroidal antiinflammatory drugs, inhibition of granulocyte elastase release from activated leukocytes may be usefu l in the prevention of these lesions. Rebamipide, a novel antiulcer ag ent, inhibited granulocyte elastase release from activated neutrophils in vitro. Rebamipide and ONO-5046, a granulocyte elastase inhibitor, markedly inhibited gastric mucosal lesion formation in rats. Gastric m yeloperoxidase activity was significantly increased 3 hr after indomet hacin administration. This increase was significantly inhibited by reb amipide and ONO-5046. Cimetidine did not inhibit granulocyte elastase- release from activated neutrophils. Although cimetidine markedly preve nted the indomethacin-induced gastric mucosal lesion formation, it did not reduce the gastric myeloperoxidase activity. Therefore, unlike ci metidine, rebamipide may prevent indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation.