A Free Radical Scavenger, Edaravone, Attenuates Steatosis and Cell Death via Reducing Inflammatory Cytokine Production in Rat Acute Liver Injury
A Free Radical Scavenger, Edaravone, Attenuates Steatosis and Cell Death via Reducing Inflammatory Cytokine Production in Rat Acute Liver Injury
复制标题
自由基清除剂依达拉奉通过减少大鼠急性肝损伤中炎症细胞因子的产生来减轻脂肪变性和细胞死亡
作者：
N. Nakamoto;S. Tada;K. Kameyama;Kumi Kitamura;S. Kurita;Yoshimasa Saito;H. Saito;H. Ishii
背景/目的：活性氧自由基在各种形式的肝损伤中起重要作用。本研究评价了新合成的自由基清除剂依达拉奉临床剂量对大鼠急性肝损伤实验模型的影响。方法：大鼠四氯化碳（CCl4）腹腔灌胃3 h后，立即静脉给药依达拉奉临床剂量（3 mg/kg）。组织学评估包括细胞凋亡和细胞因子谱检查。结果：依达拉奉可明显减轻CCl4给药后出现的脂肪变性和坏死，血清丙氨酸转氨酶和乳酸脱氢酶水平明显升高。此外，TUNEL法测定的凋亡指数在依达拉奉治疗组明显降低。CCl4给药后血清和肝脏中白细胞介素-6、肿瘤坏死因子-α、白细胞介素-4和白细胞介素-10的转录水平升高，依达拉奉治疗后降低。依达拉奉也抑制了丙二醛、4-羟基壬烯醛加合物和DNA氧化损伤标志物之一8-羟基-2′-脱氧鸟苷的形成。结论：依达拉奉对氧自由基引起的急性肝损伤具有显著的保护作用，其机制不仅可以减轻膜脂过氧化，还可以抑制炎症细胞因子的产生。我们推测依达拉奉可能对治疗各种肝损伤有临床益处。
Background/Aims: Reactive oxygen radicals play an important role in various forms of liver injury. In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats. Methods: The clinical dose of edaravone (3 mg/kg) was intravenously administered immediately and 3 h after intraperitoneal administration of carbon tetrachloride (CCl4) in rats. Histological evaluation including apoptosis and cytokine profiles were examined. Results: Fatty degeneration and necrosis with marked elevation of serum alanine aminotransferase and lactate dehydrogenase levels developed after CCl4 administration were significantly reduced by edaravone. In addition, the apoptotic index assessed by TUNEL method was significantly lowered in the edaravone treated group. Serum and liver transcription levels of interleukin-6, tumor necrosis factor-α, interleukin-4, and interleukin-10 were increased following CCl4 administration, and they were attenuated by edaravone treatment. The formation of malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, was also inhibited by edaravone treatment. Conclusion: Edaravone has a remarkable protective effect on acute liver injury caused by oxygen radicals through not only attenuating the membrane lipid peroxidation, but also inhibiting the production of inflammatory cytokines. We theorize that edaravone may have a clinical benefit in the treatment of various liver injuries.
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影响因子：
7.4
作者：
Hensley, K;Robinson, KA;Floyd, RA
通讯作者：
Floyd, RA
影响因子：
3.8
作者：
Hartley, DP;Kolaja, KL;Petersen, DR
通讯作者：
Petersen, DR
DOI：
10.1016/0748-5514(85)90026-1
发表时间：
1985-01-01
期刊：
Journal of Free Radicals in Biology and Medicine
影响因子：
--
作者：
BRATTIN W J;GLENDE E A JR;RECKNAGEL R O
通讯作者：
RECKNAGEL R O
影响因子：
29.4
作者：
CZAJA, MJ;XU, J;ALT, E
通讯作者：
ALT, E