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

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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 (100μg/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.

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Abbreviations

BrdU:

bromodeoxyuridine

CLP:

cecal ligation and puncture

Cur:

curcumin

Epo:

erythropoietin

HE:

haematoxylin and eosin (staining)

HPF:

high-power field

IL:

interleukin

NPC:

non-parenchymal cells

PH:

partial hepatectomy

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Acknowledgement

The authors cordially thank Professor Stig Bengmark, University College of London, for his exceptional help during the planning phase of the study and his continuous scientific support during its implementation.

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Authors and Affiliations

  1. Department of General-, Visceral- and Transplantation Surgery, Charité Campus Virchow, Augustenburger Platz 1, 13353,, Berlin, Germany

    Daniel Seehofer, Ulf P. Neumann, Anja Schirmeier, Jessica Carter, Si-Young Ria Cho, Andri Lederer, Nada Rayes & Peter Neuhaus

  2. Institute for Clinical and Experimental Surgery, University of Saarland, Homburg, Germany

    Michael D. Menger

  3. Department of Trauma Surgery, Klinikum Rechts der Isar, Technical University, Munich, Germany

    Andreas K. Nüssler

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  1. Daniel Seehofer
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  2. Ulf P. Neumann
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Correspondence to Daniel Seehofer.

Additional information

German Society of Surgery, Surgical Forum 2008, Best of Abstracts.

Daniel Seehofer was supported by grants from the Deutsche Forschungsgemeinschaft (Se1694/2-1).

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Seehofer, D., Neumann, U.P., Schirmeier, A. et al. Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats. Langenbecks Arch Surg 393, 325–332 (2008). https://doi.org/10.1007/s00423-008-0290-x

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