Tanaka Hiroto, Ueda Hiroki, Fukuchi Hiroko, Ichinose Masakazu
3rd Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0015, Japan.
Clin Exp Med. 2009 Sep;9(3):229-33. doi: 10.1007/s10238-009-0034-4. Epub 2009 Mar 4.
Edaravone (EDA), a newly synthesized free radical scavenger, has shown excellent results in the treatment of stroke. An overproduction of reactive oxygen species (ROS) causing oxidative DNA damage has been accounted as a major factor causing liver injury and fibrosis. Therefore, we examined its effect of EDA in rat model of liver cirrhosis induced by dimethylnitrosamine (DMN). Ten rats (DMN-group) were injected intraperitoneally with DMN (10 microg/g body weight) alone and another ten rats (EDA-group) were injected intraperitoneally with EDA (10 mg/kg body weight) 2 h after being injected with DMN. Both groups underwent their injection regimen three times a week for 4 weeks, after which the rats were sacrificed and their liver tissue sections were stained with Azan-Mallory for quantitative analyses of fibrosis development, using soft imaging and a previously published scoring system. Additionally, these sections were immunohistochemically stained using an antibody against alpha-smooth muscle actin (alpha-SMA). The total-bililubin in the EDA-group was found to be lower than that in the DMN-group. Quantitive analysis of liver fibrosis showed that the fibrotic area of the EDA-group was significantly smaller than that of the DMN-group. Additionally, the number of alpha-SMA positive cells in the EDA-group were significantly lower than that in the DMN-group. This study showed that EDA reduces liver fibrosis in a rat of cirrhosis induced by DMN. These data suggest that the reduction of liver fibrosis by EDA may be induced by the suppression of activated hepatic stellate cells.
依达拉奉（EDA）是一种新合成的自由基清除剂，已在中风治疗中显示出优异的效果。活性氧（ROS）过量产生导致氧化性DNA损伤，这被认为是引起肝损伤和肝纤维化的主要因素。因此，我们研究了依达拉奉在二甲基亚硝胺（DMN）诱导的大鼠肝硬化模型中的作用。十只大鼠（DMN组）仅腹腔注射DMN（10微克/克体重），另外十只大鼠（EDA组）在注射DMN后2小时腹腔注射依达拉奉（10毫克/千克体重）。两组每周进行三次注射方案，共4周，之后处死大鼠，其肝组织切片用偶氮马洛里染色法染色，以使用软组织成像和先前发表的评分系统对纤维化发展进行定量分析。此外，这些切片用抗α平滑肌肌动蛋白（α-SMA）抗体进行免疫组织化学染色。发现EDA组的总胆红素低于DMN组。肝纤维化的定量分析表明，EDA组的纤维化面积明显小于DMN组。此外，EDA组中α-SMA阳性细胞的数量明显低于DMN组。本研究表明，依达拉奉可减轻DMN诱导的大鼠肝硬化中的肝纤维化。这些数据表明，依达拉奉减轻肝纤维化可能是通过抑制活化的肝星状细胞来实现的。
