Mycophenolate mofetil attenuates liver ischemia/reperfusion injury in rats.
Mycophenolate mofetil (MMF) has been gradually introduced into clinical liver transplantation in recent years. However, the effects of MMF on hepatic ischemia/reperfusion (I/R) injury and the potential mechanisms involved are not totally understood. We aimed to evaluate whether MMF could attenuate hepatic I/R injury. MMF (20 mg/kg) or vehicle was administered to Wistar rats by gavage. The rats were then subjected to hepatic ischemia. Liver cell apoptosis and the levels of aspartate aminotransferase, myeloperoxidase (MPO), xanthine oxidase (XOD) and malondialdehyde (MDA) were determined. Expression of vascular cell adhesion molecule-1 (VCAM-1) and activation of mitogen-activated protein kinases (MAPKs) were also investigated. Furthermore, the hepatic microcirculation was observed by intravital fluorescence microscopy. Rats pretreated with MMF exhibited significant alleviation of their postischemic liver function. Liver cell apoptosis and the tissue MPO, XOD and MDA levels were decreased by MMF pretreatment. MMF also improved I/R-induced hemodynamic turbulence, as evidenced by reduced hepatic perfusion failure and decreased numbers of rolling and adherent leukocytes. I/R injury induced activation of the MAPKs pathway while expression of VCAM-1 was downregulated by MMF pretreatment. In summary, MMF attenuates hepatic I/R injury through suppression of the production of reactive oxygen species and amelioration of postischemic microcirculatory disturbances.
Liu
Yuan-Xing
YX
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
Jin
Li-Ming
LM
Zhou
Lin
L
Xie
Hai-Yang
HY
Jiang
Guo-Ping
GP
Wang
Yan
Y
Feng
Xiao-Wen
XW
Chen
Hui
H
Yan
Sheng
S
Zheng
Shu-Sen
SS
D000818:Animals; D017209:Apoptosis; D042783:Endothelial Cells / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D008833:Microcirculation; D008856:Microscopy, Fluorescence / Q000379:methods; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy*
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D009173:Mycophenolic Acid