Rikkunsi-to Prevents Indomethacin induced Gastric Mucosal Injury by Inhibiting Activation of Leukocytes / 日本東洋医学雑誌

ABSTRACT

Granulocyte elastase released from activated leukocytes plays an important role in leukocyte infiltration. Since activated leukocytes have been shown to be involved in the pathogenesis of gastric mucosal lesion formation induced by indomethacin, inhibition of granulocyte elastase release from activated leukocytes may be useful in the prevention of these lesions. Rikkunsi-to and ONO-5046, a granulocyte elastase inhibitor, markedly inhibited gastric mucosal lesion formation in rats. Gastric myeloperoxidase activity was significantly increased 3 hours after indomethacin administration. This increase was significantly inhibited by Rikkunsi-to and ONO-5046. Rikkunsi-to inhibited granulocyte elastase release from activated neutrophils in vitro while cimetidine did not. Although cimetidine markedly prevented the indomethacin-induced gastric mucosal lesion formation, it did not reduce gastric myeloperoxidase activity. Therefore, unlike cimetidine, Rikkunsi-to may prevent indomethacin-induced gastric mucosal lesion formation by inhibiting neutrophil activation.