title: Erythropoietin promotes hepatic regeneration after extended liver resection in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of General, Visceral and Transplantation Surgery at Charité, Campus Virchow Klinikum, Universitaetsmedizin Berlin, Germany. maximilian.schmeding@charite.de
authors: Maximilian
authors: M
authors: Schmeding
authors: Sabine
authors: S
authors: Boas-Knoop
authors: Steffen
authors: S
authors: Lippert
authors: Martin
authors: M
authors: Ruehl
authors: Radjan
authors: R
authors: Somasundaram
authors: Tarkan
authors: T
authors: Dagdelen
authors: Peter
authors: P
authors: Neuhaus
authors: Ulf P
authors: UP
authors: Neumann
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006498:Hepatectomy; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D023421:Models, Animal; D011169:Portal Vein; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin