Edaravone reduces ischemia-reperfusion injury mediators in rat liver.
BACKGROUND
In hepatic ischemia-reperfusion (I/R) injury, oxidative stress both directly injures the liver and promotes an inflammatory reaction by up-regulating various inflammatory mediators. We investigated whether edaravone, a new hydroxy radical scavenger, could reduce hepatic I/R injury including expression of inflammatory mediators such as cytokines and adhesion molecules.


METHODS
Male Sprague-Dawley rats were subjected to 30 min of partial hepatic pedicle clamping (70%) followed by reperfusion. Just after initiation of reperfusion and again 1 h later, edaravone was administered intraportally. After reperfusion hepatic lipid peroxidation was measured by thiobarbituric acid assay, and hepatic injury was quantified by measuring hepatic enzymes in plasma. We serially quantified hepatic expression of mRNAs for tumor necrosis factor (TNF)-alpha and E-selectin, and histologically examined E-selectin expression and neutrophil accumulation.


RESULTS
In the edaravone group, hepatic lipid peroxidation and hepatic enzyme leakage were significantly less than in the saline group. Hepatic expression of TNF-alpha and E-selectin mRNAs was significantly lower in the edaravone than the saline group, at 2 h after initiation of reperfusion. Histologically, E-selectin immunoreactivity and neutrophil accumulation were less evident in hepatic sections from the edaravone group.


CONCLUSIONS
Edaravone reduced hepatic I/R injury by minimizing oxidative stress, and inhibited subsequent injurious inflammation by reducing expression of inflammatory cytokines and adhesion molecules.
Taniguchi
Masanobu
M
Second Department of Surgery, Faculty of Medical Sciences, University of Fukui, Shimoaizuki, Fukui, Japan. tanibee@hotmail.co.jp
Uchinami
Masaru
M
Doi
Koji
K
Yoshida
Makoto
M
Sasaki
Hisashi
H
Tamagawa
Koji
K
Horiuchi
Tetsuya
T
Tanaka
Kuniyoshi
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D019040:E-Selectin / Q000235:genetics; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D019040:E-Selectin; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000077553:Edaravone; D000983:Antipyrine