Mycophenolate mofetil attenuates liver ischemia/reperfusion injury in rats
Open Access
- 4 June 2009
- journal article
- Published by Frontiers Media SA in Transplant International
- Vol. 22 (7), 747-756
- https://doi.org/10.1111/j.1432-2277.2009.00866.x
Abstract
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.Keywords
This publication has 43 references indexed in Scilit:
- FTY720 Improves Survival After Transient Ischemia and Reperfusion of the Hind LimbsJournal Of Trauma-Injury Infection and Critical Care, 2007
- The effect of estrogen on hepatic microcirculation after ischemia/reperfusionInternational Journal of Colorectal Disease, 2007
- Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega-3 fatty acidsHepatology, 2007
- Analysis of clinical variables of donors and recipients with respect to short-term graft outcome in human liver transplantationTransplantation Proceedings, 2004
- Rat liver ischemia–reperfusion-induced apoptosis and necrosis are decreased by FK506 pretreatmentEuropean Journal of Pharmacology, 2003
- Preconditioning protects liver and lung damage in rat liver transplantation: Role of xanthine/xanthine oxidaseHepatology, 2002
- Ischemic preconditioning: a defense mechanism against the reactive oxygen species generated after hepatic ischemia reperfusion1Transplantation, 2002
- Immunosuppressants Decrease Neutrophil Chemoattractant and Attenuate Ischemia/Reperfusion Injury of the Liver in RatsJournal Of Trauma-Injury Infection and Critical Care, 1998
- MYCOPHENOLATE MOFETIL IN RENAL ALLOGRAFT RECIPIENTSTransplantation, 1997
- Oxygen-Derived Free Radicals in Postischemic Tissue InjuryNew England Journal of Medicine, 1985