Antifibrotic effect of edaravone in rat liver cirrhosis induced by dimethylnitrosamine.
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.
Tanaka
Hiroto
H
3rd Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0015, Japan. makoayu@wakayama-med.ac.jp
Ueda
Hiroki
H
Fukuchi
Hiroko
H
Ichinose
Masakazu
M
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D004128:Dimethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006651:Histocytochemistry / Q000379:methods; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D012720:Severity of Illness Index
D016166:Free Radical Scavengers; D004128:Dimethylnitrosamine; D001663:Bilirubin; D000077553:Edaravone; D000983:Antipyrine