Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats
Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats
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DOI：
10.1016/j.jhep.2004.09.018
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发表时间：
2005-01-01
影响因子：
25.7
通讯作者：
Kamiyama, Y
中科院分区：
文献类型：
--
作者：
Tsuji, K;Kwon, AH;Kamiyama, Y
背景/目的：大型手术（例如大规模肝切除术）后的感染会引起肝功能障碍，有时会导致多器官衰竭和死亡。我们通过大鼠部分肝切除术后内毒素血症实验模型证明了新合成的自由基清除剂3-甲基-1-苯基-2-吡唑啉-5-酮（依达拉奉）的抗炎作用和功能机制。方法：70%肝切除术后48小时给予大鼠脂多糖（LPS）治疗。 LPS治疗前静脉注射依达拉奉。结果：依达拉奉显着提高LPS治疗大鼠肝切除术后的存活率，并抑制血清AST和LDH水平的升高。组织病理学分析表明，依达拉奉可预防肝脏、肾脏和脾脏的炎症变化。依达拉奉抑制氧化损伤标志物之一丙二醛的形成。依达拉奉治疗组抑制了血清和肝组织中炎症细胞因子和细胞因子诱导的中性粒细胞趋化剂（CINC）的增加。电泳迁移率变动分析表明，依达拉奉抑制转录因子核因子 kappa B (NF-kappaB) 的激活。依达拉奉还可以减少诱导型一氧化氮合酶 (iNOS) 的诱导。 结论：依达拉奉不仅通过减轻氧化损伤，还通过减少炎症细胞因子、CINC 和 iNOS 的产生（部分通过抑制 NF-κB 激活）来预防部分肝切除术后内毒素诱导的肝损伤。 (C) 2004 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background/Aims: Infection after major surgery, such as massive hepatectomy, induces liver dysfunction, occasionally leading to multiple organ failure and death. We demonstrated the anti-inflammatory effects and functional mechanisms of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a newly synthesized free radical scavenger, on an experimental model of endotoxemia after partial hepatectomy in rats.Methods: Rats were treated with lipopolysaccharide (LPS) 48h after 70% hepatectomy. Edaravone was administered intravenously before LPS-treatment.Results: Edaravone markedly improved the survival rate of LPS-treated rats after hepatectomy and inhibited increases in serum levels of AST and LDH. Histopathological analysis demonstrated that edaravone prevented inflammatory changes in the liver, kidney and spleen. Edaravone inhibited the formation of one of the markers of oxidative damage, malondialdehyde. Increases in inflammatory cytokines and cytokine-induced neutrophil chemoattractant (CINC) in serum and liver tissue were inhibited in the edaravone-treated group. An electrophoretic mobility shift assay revealed that edaravone inhibited the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB). Edaravone also reduced the induction of inducible nitric oxide synthase (iNOS).Conclusions: Edaravone prevents endotoxin-induced liver injury after partial hepatectomy not only by attenuating oxidative damage, but also by reducing the production of inflammatory cytokines, CINC and iNOS, in part through the inhibition of NF-kappaB activation. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.