Erythropoietin promotes hepatic regeneration after extended liver resection in rats
- 16 July 2008
- journal article
- Published by Wiley in Journal of Gastroenterology and Hepatology
- Vol. 23 (7pt1), 1125-1131
- https://doi.org/10.1111/j.1440-1746.2007.05265.x
Abstract
It has been proven in various animal studies that recombinant human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as hepatic, tissue from ischemia, and promotes regeneration of adult central nervous system neurons. To date, no data are available as to whether rHuEPO has the ability to stimulate liver regeneration after liver resection. Rats undergoing 70% or 90% hepatectomy received an intraportalvenous administration (i.p.) of rHuEPO prior to resection or a subcutaneous injection (s.c.) for 3 days postoperatively, control animals were treated with surgery and saline injection only. Regeneration capacity of remnant livers was studied over 7 days by histology and immunohistochemistry (Ki-67, proliferating cell nuclear antigen [PCNA]). Polymerase chain reaction was carried out to measure transforming growth factor beta (TGF-beta), hypoxia induced factor (HIF), signal transducing activator 3 and vascular endothelial growth factor. Ten-day survival in rats undergoing 90% hepatectomy significantly increased in i.p.-pretreated animals. After 70% hepatectomy the mitotic index was significantly increased in both rHuEPO-treated groups. These data were confirmed by PCNA and Ki-67 expression, which was significantly increased in the treated groups 24 h and 2 days after liver resection. TGF-beta and HIF mRNA both were upregulated in control animals 3 h after surgery. rHuEPO effectively increased liver regeneration in rats after 70% liver resection and enhanced survival after 90% hepatectomy. Thus, rHuEPO may increase the regenerative capacity after major hepatectomy.Keywords
This publication has 33 references indexed in Scilit:
- Mechanisms of Hepatic Regeneration Following Portal Vein Embolization and Partial Hepatectomy: A ReviewWorld Journal of Surgery, 2007
- Critical Appraisal of the Clinical and Pathologic Predictors of Survival After Resection of Large Hepatocellular CarcinomaArchives of Surgery, 2005
- Portal Application of Autologous CD133 + Bone Marrow Cells to the Liver: A Novel Concept to Support Hepatic RegenerationThe International Journal of Cell Cloning, 2005
- The Erythropoietin Receptor and Its Expression in Tumor Cells and Other TissuesThe Oncologist, 2004
- The Effect of Erythropoietin on Allogeneic Blood Requirement in Patients Undergoing Elective Liver Resection: A Model SimulationAnesthesia & Analgesia, 2004
- Hepatocyte growth factor/c-metsignaling pathway is required for efficient liver regeneration and repairProceedings of the National Academy of Sciences of the United States of America, 2004
- A 3‐year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusionLiver International, 2003
- Fatty Liver in Liver Transplantation and SurgerySeminars in Liver Disease, 2001
- Reduction of transfusion requirements during major hepatic resection for metastatic diseaseSurgery, 1999
- Plenary lecture. The molecular biology erythropoietinNephrology Dialysis Transplantation, 1999