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


METHODS
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.
Ji
Yuan
Y
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
Dahmen
Uta
U
Madrahimov
Nodir
N
Madrahimova
Fotima
F
Xing
Wei
W
Dirsch
Olaf
O
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division; D004261:DNA Replication; D000069585:Filgrastim; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006498:Hepatectomy / Q000009:adverse effects* / Q000379:methods; D022781:Hepatocytes / Q000166:cytology; D008026:Ligation; D017093:Liver Failure / Q000209:etiology / Q000517:prevention & control; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000187:drug effects; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D008562:Membrane Glycoproteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D000099231:Lipopolysaccharide-Binding Protein