REBAMIPIDE PREVENTS INDOMETHACIN-INDUCED GASTRIC-MUCOSAL LESION FORMATION BY INHIBITING ACTIVATION OF NEUTROPHILS IN RATS

Since granulocyte elastase has been shown to be involved in the pathog enesis of gastric mucosal lesion formation induced by nonsteroidal ant iinflammatory drugs, inhibition of granulocyte elastase release from n eutrophils may be useful in the prevention of these lesions. The objec tive of this study was to determine whether rebamipide inhibits neutro phil activation in vivo and in vitro. Rebamipide and ONO-5046, a speci fic granulocyte elastase inhibitor, markedly inhibited indomethacin-in duced mucosal injury in rats. Gastric myeloperoxidase activity was sig nificantly increased 3 h after indomethacin administration. This incre ase was significantly inhibited by rebamipide and ONO-5046, Although c imetidine markedly prevented the indomethacin-induced mucosal lesion f ormation, it did not reduce the gastric myeloperoxidase activity. Reba mipide inhibited granulocyte elastase release from neutrophils in vitr o by inhibiting the increase in intracellular Ca2+ level. Cimetidine d id not inhibit granulocyte elastase release from neutrophils. Furtherm ore, the elevation of intracellular Ca2+ level was not inhibited by ci metidine. Therefore, unlike cimetidine, rebamipide may prevent indomet hacin-induced mucosal injury by inhibiting neutrophil activation.