The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats.
BACKGROUND
The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) have been shown to promote liver regeneration after major hepatectomy.Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy.


METHODS
Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21) that received normal saline, an EPO group (n = 21), that received EPO 500 IU/kg, a GM-CSF group (n = 21) that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21) which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67.


RESULTS
Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p < 0.01). When administering both, the effect of EPO seems to fade as EPO and GM-CSF treated rats have decreased regeneration compared to EPO administration alone (p < 0.01).


CONCLUSIONS
EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.
Vassiliou
Ioannis
I
Experimental Surgical Unit, 2nd Department of Surgery, Medical School, University of Athens, Aretaieion Hospital, Athens 11528, Greece. ianvass@otenet.gr
Lolis
Evangelos
E
Nastos
Constantinos
C
Tympa
Aliki
A
Theodosopoulos
Theodosios
T
Dafnios
Nikolaos
N
Fragulidis
George
G
Frangou
Matrona
M
Kondi-Pafiti
Agathi
A
Smyrniotis
Vassilios
V
D000818:Animals; D001835:Body Weight; D004338:Drug Combinations; D004921:Erythropoietin / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006498:Hepatectomy; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D011184:Postoperative Period; D057234:Preoperative Period; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004338:Drug Combinations; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor