Erythropoietin reduces ischemia-reperfusion injury after fatty liver transplantation in rats

Abstract

Introduction: Liver transplantation (LT) remains the only curative option for treatment of liver cirrhosis today. However, the scarcity of available adequate donor organs accounts for a major challenge in virtually all transplant programs around the globe. Therefore, the enlargement of the so-called „donor pool“ by organs which normally would be regarded as inadequate offers a potential solution to the problem. The reduction of ischemia-reperfusion injury may enable potentially inferior grafts to perform satisfactory after transplantation. In the past, our group and others have demonstrated that erythropoietin (epo) reduces ischemia-reperfusion injury in rat livers and other organs such as brain, heart and kidney. Materials and Methods: In 60 Wistar rats fatty livers were induced by a special diet. These livers were transplanted into 60 recipient rats after perfusion with UW solution and cold ischemic time of 6 hours. 30 rats were treated with injection of 4.000 IU/kg of epo into the portal vein at reperfusion (additional injection of 4.000 IU/kg in donor animals before organ removal), while 30 animals received injection of the identical volume of saline at the same time points (controls). 2, 4.5, 24, 48 hours and 7 days after reperfusion we analysed organ function and tissue damage by AST, ALT, LDH, GLDH values as well as histological screening for apoptosis and necrosis (H/E, PAS, TUNEL, Hypoxyprobe). Results: In contrast to our data on non-fatty liver transplantation we did not detect significant differences in the enzyme levels at any time points between epo-treated and untreated animals. However, we did find a dramatic reduction in apoptosis and necrosis rates among epotreated animals, especially in the first 24 hours after reperfusion. Hypoxyprobe staining displayed a significantly smaller number of hypoxic cells in epo-treated liver tissue. 7-day survival was also increased in the epo-group. Conclusion: Erythropoietin enhances the postoperative liver function by reduction of hepatocellular apoptosis and necrosis after transplantation of fatty livers in rats.