The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury
The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury
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DOI：
10.1002/bjs.4401
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发表时间：
2004-02-01
影响因子：
9.6
通讯作者：
Maehara, Y
中科院分区：
文献类型：
--
作者：
Ninomiya, M;Shimada, M;Maehara, Y
背景：氧化应激以双相模式参与肝脏缺血再灌注（IR）损伤。除了直接的细胞毒性作用外，氧化应激还启动促进第二阶段肝损伤的信号转导过程。本研究探讨了羟基自由基清除剂MCI-186对肝脏冷IR损伤的双相过程的影响。方法：大鼠肝脏冷保存16 h后，在离体肝脏灌注系统上用含氧Krebs-Henseleit碳酸氢盐缓冲液再灌注120 min。连续获得灌注液样本，并记录门静脉流速。为了确定MCI-186是否影响控制第二阶段损伤的细胞因子水平，在灌注液中测量白细胞介素（IL）10和肿瘤坏死因子（TNF）α的水平。向灌注液中添加1 mg/l MCI-186可显着改善门静脉流量（P <0.050）、肝酶释放量（P = 0.038）、总胆汁生成量（P = 0.029）和丙二醛（P = 0.038）。此外，用MCI-186处理导致IL-10释放的显著增加（P = 0.032）。结论：MCI-186，一种可供临床使用的药物，似乎对肝脏冷IR损伤有直接和间接的保护作用。
Background: Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury.Methods: After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate.Results: Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P < 0.050), hepatic enzyme release into the perfusate (P = 0.038), total bile production (P = 0.029) and malondialdehyde concentration (P = 0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P = 0.032). TNF-alpha levels were not affected.Conclusions: MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.