The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury.
BACKGROUND
Oxidative stress contributes to hepatic ischaemia-reperfusion (IR) injury in a biphasic pattern. In addition to direct cytotoxic effects, oxidative stress also initiates the signal transduction processes that promote second-phase liver injury. The present study investigated the effects of the hydroxyl radical scavenger MCI-186 on the biphasic process of hepatic cold IR injury.


METHODS
After cold preservation for 16 h, rat livers were reperfused on an isolated liver perfusion system for 120 min with oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. To determine whether MCI-186 affected cytokine levels that control the second-phase injury, levels of interleukin (IL) 10 and tumour necrosis factor (TNF) alpha were measured in the perfusate.


RESULTS
Addition of MCI-186 1 mg/l into the perfusate significantly improved portal flow (P<0.050), hepatic enzyme release into the perfusate (P=0.038), total bile production (P=0.029) and malondialdehyde concentration (P=0.038). Furthermore, treatment with MCI-186 led to a substantial increase in IL-10 release (P=0.032). TNF-alpha levels were not affected.


CONCLUSIONS
MCI-186, an agent ready for clinical use, appears to have direct and indirect protective effects against hepatic cold IR injury.
Ninomiya
M
M
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. nnmym@surg2.med.kyushu-u.ac.jp
Shimada
M
M
Harada
N
N
Soejima
Y
Y
Suehiro
T
T
Maehara
Y
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003080:Cold Temperature / Q000009:adverse effects*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D017665:Hydroxyl Radical; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000098:blood supply*; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D015430:Weight Gain
D016166:Free Radical Scavengers; D012333:RNA, Messenger; D016753:Interleukin-10; D017665:Hydroxyl Radical; D000077553:Edaravone; D000983:Antipyrine