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

Langenbecks Arch Surg. 2008 May;393(3):325-32. doi: 10.1007/s00423-008-0290-x. Epub 2008 Feb 27.

Abstract

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 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.

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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / pharmacology*
  • Cell Division / drug effects
  • Curcumin / pharmacology*
  • Drug Administration Schedule
  • Drug Synergism
  • Erythropoietin / pharmacology*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Injections, Intraperitoneal
  • Intestinal Perforation / pathology
  • Liver Function Tests
  • Liver Regeneration / drug effects*
  • Organ Size / drug effects
  • Peritonitis / pathology
  • Premedication
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Sepsis / pathology

Substances

  • Antioxidants
  • Recombinant Proteins
  • Erythropoietin
  • Granulocyte Colony-Stimulating Factor
  • Curcumin