Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats.
BACKGROUND
The effect of erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) alone or in combination with the hepatoprotective antioxidant curcumin (Cur) was evaluated in a model of delayed liver regeneration.


METHODS
Sprague Dawley rats underwent 70% liver resection with simultaneous cecal ligation and puncture and were randomised to five groups: no treatment, G-CSF (100 microg/kg), Epo (1,000 IU/kg), each alone or in combination with Cur (100mg/kg). Twenty-four hours after surgery, blood and tissue samples were collected. Markers of liver regeneration (liver weight, mitotic index, Ki-67 index), function (bilirubin, bile flow) and hepatocellular damage (liver enzymes, histomorphology) were determined. In addition, cytokine expression and hepatic glutathione concentrations were measured.


RESULTS
Liver regeneration was not improved by G-CSF or Epo monotherapy. Epo more effectively increased liver weight and regeneration markers, but the difference was not significant. Whereas liver regeneration was slightly inhibited in the G-CSF plus Cur group, Epo plus Cur significantly improved liver regeneration. This was accompanied by reduced oxidative stress. Liver function and the expression of pro-inflammatory cytokines were comparable in all treatment groups.


CONCLUSIONS
In the present model, Epo, at a relatively low dosage, did not improve liver regeneration. However, the combination of Epo and Cur showed a synergistic effect with highly significant stimulation of liver regeneration.
Seehofer
Daniel
D
Department of General-, Visceral- and Transplantation Surgery, Charité Campus Virchow, Berlin, Germany. daniel.seehofer@charite.de
Neumann
Ulf P
UP
Schirmeier
Anja
A
Carter
Jessica
J
Cho
Si-Young Ria
SY
Lederer
Andri
A
Rayes
Nada
N
Menger
Michael D
MD
Nüssler
Andreas K
AK
Neuhaus
Peter
P
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004921:Erythropoietin / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007416:Intestinal Perforation / Q000473:pathology; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010538:Peritonitis / Q000473:pathology; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018805:Sepsis / Q000473:pathology
D000975:Antioxidants; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D003474:Curcumin