Mechanism of Superoxide Generation System in Indomethacin-Induced Gastric Mucosal Injury in Rats

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We studied the mechanism of the superoxide generation system in indomethacin-induced gastric mucosal injury. First, 10mM indomethacin had no direct effect on xanthine oxidase (XOD) activity. Next, we found that NADPH oxidase activity in polymorphonuclear leukocytes (PMN) of peripheral blood was significantly increased 6h after administration of indomethacin. This phenomenon was inhibited by the injection of the NADPH oxidase inhibitor, diphenylene iodonium chloride (DIC). Activation of NADPH oxidase caused the component, p47^<phox> to be translocated to the plasma membrane. Since indomethacin did not directly activate NADPH oxidase, we sought another route of activation of PMN. As IL-1 and TNF α play in the inflammation, we examined these cytokines in this study. TNF α was not detected but IL-1 was increased significantly 30min after administration of indomethacin.
公益社団法人日本薬学会の論文
2001-02-01