Multiple Doses of Erythropoietin Impair Liver Regeneration by Increasing TNF-α, the Bax to Bcl-xL Ratio and Apoptotic Cell Death

摘要: Background Liver resection and the use of small-for-size grafts are restricted by necessity to provide a sufficient amount functional liver mass. Only few promising strategies maximize regeneration available. Apart from its erythropoiesis-stimulating effect, erythropoietin (EPO) has meanwhile been recognized as mitogenic, tissue-protective, anti-apoptotic pleiotropic cytokine. Thus, EPO may support hepatic tissue. Methodology Rats undergoing 68% hepatectomy received daily either high dose (5000 IU/kg bw iv) or low (500 recombinant human equal amounts physiologic saline. Parameters hepatocellular apoptosis were assessed at 24 h, 48 h 5 d after resection. In addition, red blood cell count, hematocrit serum levels well plasma concentrations TNF-α IL-6 evaluated. Further, Bcl-xL Bax protein expression analyzed Western blot. Principal Findings Administration significantly reduced PCNA followed significant decrease in restitution mass day partial hepatectomy. increased shifted ratio towards pro-apoptotic resulting apoptosis. Conclusions Multiple doses increase impair rats. careful consideration should be made pre- post-operative administration setting transplantation.