Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats

Introduction 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. Materials and 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 mu g/kg), Epo (1,000IU/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. Conclusion 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.