Edaravone protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat liver.
This study investigated the effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, MCI-186), a potent free radical scavenger, on the prevention of mitochondrial injury induced by hepatic ischemia and reperfusion. Mature male rats were subjected to 70 min of hepatic ischemia and 2 h of reperfusion. The rats received vehicle or edaravone (10 mg/kg body weight) intravenously prior to ischemia, before reperfusion and 1 h after reperfusion. In the vehicle-treated animals, the respiratory control index, ADP/O, State 3 respiration and dinitrophenol-induced uncoupled respiration decreased markedly after ischemia/reperfusion and were restored by edaravone administration. Mitochondrial lipid peroxidation was elevated in the vehicle-treated group, which was attenuated by edaravone, while mitochondrial glutathione peroxidase activity decreased in the vehicle-treated group, which was similarly abrogated by edaravone treatment. Electron microscopic observation demonstrated that treatment with edaravone restored the ischemia/reperfusion-induced disorganization of mitochondrial structures. Edaravone protects against mitochondrial injury, which prevents mitochondrial oxidative stress and improves ischemia/reperfusion-induced hepatic energy metabolism.
Okatani
Yuji
Y
Department of Clinical Nursing Science, Kochi Medical School, Oko, Nankoku, Kochi 783-8505, Japan. okataniy@med.kochi-ms.ac.jp
Wakatsuki
Akihiko
A
Enzan
Hideaki
H
Miyahara
Yasuyo
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000077553:Edaravone; D004579:Electron Transport / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase; D000077553:Edaravone; D000983:Antipyrine