MCI-186 (edaravone), a free radical scavenger, attenuates hepatic warm ischemia-reperfusion injury in rats.
Hepatic warm ischemia-reperfusion injury (IRI) during hepatectomy and liver transplantation is a major cause of liver dysfunction in which the pathologic role of free radicals is a major concern. To assess the effect of MCI-186 (edaravone) on hepatic IRI, male Wistar rats were subjected to partial hepatic ischemia for 60 min after pretreatment with vehicle (group C) or MCI-186 (group M), or after both MCI-186 pretreatment and additional administration of MCI-186 12 h after reperfusion (group MX). Groups M and MX showed significantly lower levels of serum alanine aminotransferase and hepatic lipid peroxidation than group C, and also significantly lower expression levels of mRNA for cytokines, chemokines and intercellular adhesion molecule-1. There were fewer tissue monocytes and neutrophils in groups M and MX than in group C. These effects were more marked in group MX than in group M. Our findings suggest that treatment with MCI-186 attenuates hepatic IRI in this rat in vivo model.
Suzuki
Fumitaka
F
Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Asahi, Matsumoto, Japan.
Hashikura
Yasuhiko
Y
Ise
Hirohiko
H
Ishida
Akiko
A
Nakayama
Jun
J
Takahashi
Masafumi
M
Miyagawa
Shin-Ichi
S
Ikeda
Uichi
U
D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D000447:Aldehydes; D018925:Chemokines; D016207:Cytokines; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D000410:Alanine Transaminase; C027576:4-hydroxy-2-nonenal; D000077553:Edaravone; D000983:Antipyrine