Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat.
Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.
Ninomiya
Mizuki
M
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nnmym@ surg2.med.kyushu-u.ac.jp.
Shimada
Mitsuo
M
Harada
Noboru
N
Shiotani
Satoko
S
Hiroshige
Shoji
S
Soejima
Yuji
Y
Suehiro
Taketoshi
T
Sugimachi
Keizo
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017209:Apoptosis; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine