Nakamoto Nobuhiro, Tada Shinichiro, Kameyama Kaori, Kitamura Kumi, Kurita Satoshi, Saito Yoshimasa, Saito Hidetsugu, Ishii Hiromasa
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Free Radic Res. 2003 Aug;37(8):849-59. doi: 10.1080/1071576031000136586.
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.
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.
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-alpha, 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.
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.
背景/目的：活性氧自由基在各种肝损伤形式中起重要作用。在本研究中，我们评估了新合成的自由基清除剂依达拉奉在临床剂量下对大鼠急性肝损伤实验模型的疗效。
在大鼠腹腔注射四氯化碳（CCl4）后立即及3小时后静脉注射依达拉奉临床剂量（3mg/kg）。进行包括凋亡和细胞因子谱在内的组织学评估。
依达拉奉显著减轻了CCl4给药后出现的脂肪变性和坏死，同时血清丙氨酸转氨酶和乳酸脱氢酶水平显著升高。此外，依达拉奉治疗组通过TUNEL法评估的凋亡指数显著降低。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，而依达拉奉治疗使其减弱。依达拉奉治疗还抑制了丙二醛、4-羟基壬烯醛加合物以及氧化DNA损伤标志物之一8-羟基-2'-脱氧鸟苷的形成。
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，不仅通过减轻膜脂质过氧化，还通过抑制炎性细胞因子的产生。我们推测依达拉奉在治疗各种肝损伤方面可能具有临床益处。
