Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

作     者：Kazuaki Tejima Masahiro Arai Hitoshi Ikeda Tomoaki Tomiya Mikio Yanase Yukiko Inoue Takako Nishikawa Naoko Watanabe Natsuko Ohtomo Masao Omata Kenji Fujiwara 

作者机构：Department of Gastroenterology University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-8655 Japan Department of Gastroenterology Toshiba General Hospital 6-3-22 Higashiooi Shinagawa-ku Tokyo 140-8522 Japan Yokohama Rosai Hospital 3211 Kozukue-cho Kouhoku-ku Yokohama-shi Kanagawa 222-0036 Japan 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第38期

页      面：5071-5078页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported in part by Grant-in-Aid for Scientific Research No. 17590615 to K. T. from Japan Society for the Promotion of Science 

主　　题：Diphenyieneiodonium chioride Ischemia/ reperfusion injury Ischemic preconditioning Liver transplantation Oxygen radicals 

摘      要：AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.