G-CSF administration in a small-for-size liver model

J Invest Surg. 2009 May-Jun;22(3):167-77. doi: 10.1080/08941930802713027.

Abstract

Background: Extended liver resection is applied in the treatment of liver tumors and during living-related liver transplantation. This procedure can lead to transient, in some patients even lethal liver failure. Administration of G-CSF is associated with an increased survival after toxic liver damage. It is the aim of this study to test the effect of G-CSF administration in the rat 90% extended liver resection model.

Materials: Rats with and without G-CSF treatment were subjected to 90% partial hepatectomy using a mass ligation technique. Animals were sacrificed 6 hr, 24 hr, and 7 days after resection. Read-out parameters were liver damage in terms of liver enzymes and histomorphological alterations. Hepatic regeneration was determined by measuring liver weight recovery and calculating the BrdU proliferation index of hepatocytes. G-CSF-receptor expression was visualized in both groups by immunohistochemistry. Expression of lipopolysaccharide-binding-protein (LBP) mRNA was evaluated by quantitative PCR.

Results: Survival rate was increased in the G-CSF-treatment group. Full liver weight recovery within one week was only achieved in the treatment group and was accompanied by reduced liver damage. G-CSF-receptor upregulation subsequent to administration of G-CSF may indicate a direct receptor mediated effect of G-CSF on the liver. Upregulation of LBP mRNA in the liver of G-CSF treated animals--reported to be associated with an increased host defense--could demonstrate a mode of action of G-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cell Division
  • DNA Replication
  • Filgrastim
  • Gene Expression Profiling
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hepatectomy / adverse effects*
  • Hepatectomy / methods
  • Hepatocytes / cytology
  • Ligation
  • Liver Failure / etiology
  • Liver Failure / prevention & control
  • Liver Regeneration / drug effects
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Organ Size / drug effects
  • Random Allocation
  • Rats
  • Rats, Inbred Lew
  • Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
  • Receptors, Granulocyte Colony-Stimulating Factor / genetics
  • Recombinant Proteins
  • Up-Regulation / drug effects

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Membrane Glycoproteins
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Recombinant Proteins
  • lipopolysaccharide-binding protein
  • Granulocyte Colony-Stimulating Factor
  • Filgrastim