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Updated: Jun 22, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Mycophenolate mofetil attenuates liver ischemia/reperfusion injury in rats
Yuan-Xing Liu1, Li-Ming Jin, Lin Zhou
1Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China.
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.
Insights
Mycophenolate mofetil (MMF) protects against liver injury after ischemia and reperfusion. This immunosuppressant reduces cell death, oxidative stress, and improves blood flow in the liver.
Area of Science:
- Hepatology
- Immunology
- Transplantation Surgery
Background:
- Hepatic ischemia/reperfusion (I/R) injury is a significant complication in liver transplantation.
- The precise mechanisms by which immunosuppressants like MMF impact I/R injury require further elucidation.
Purpose of the Study:
- To investigate the protective effects of mycophenolate mofetil (MMF) against hepatic I/R injury in a rat model.
- To explore the underlying mechanisms, including oxidative stress, inflammation, and microcirculatory disturbances.
Main Methods:
- Wistar rats were pretreated with MMF (20 mg/kg) or vehicle before undergoing hepatic ischemia.
- Assessed liver function, apoptosis, and levels of MPO, XOD, and MDA.
- Investigated VCAM-1 expression and MAPK activation.
- Observed hepatic microcirculation using intravital fluorescence microscopy.
Main Results:
- MMF pretreatment significantly improved postischemic liver function.
- Reduced liver cell apoptosis and decreased levels of MPO, XOD, and MDA.
- Improved microcirculation by reducing leukocyte adhesion and rolling, and mitigating perfusion failure.
- Downregulated VCAM-1 expression and suppressed MAPK activation.
Conclusions:
- MMF attenuates hepatic I/R injury in rats.
- The protective effects are mediated by suppressing reactive oxygen species production and improving postischemic microcirculatory disturbances.
- MMF demonstrates potential as a therapeutic agent to mitigate liver injury in transplantation settings.
