Granulocyte colony-stimulating factor administration reverses cadmium-associated inhibition of hepatocyte regeneration.
OBJECTIVE
To document whether the administration of granulocyte colony-stimulating factor (G-CSF) enhances the impaired regenerative response of hepatocytes to partial hepatectomy (PH), in cadmium-pretreated partially hepatectomized rats.


METHODS
Rats were injected intraperioneally with 2.5 mg CdCl2/kg body weight, 24h before PH. G-CSF (1500 or 150 micrograms/kg body weight) or saline was administered intraperitoneally in cadmium-pretreated partially hepatectomized rats at the same time as PH. The liver regenerative process was estimated 24h after PH. [3H] thymidine incorporation into liver DNA, liver thymidine kinase (TK) activity, mitotic index and proliferating cell nuclear antigen (PCNA) immunostaining were used as indices of hepatocyte proliferation.


RESULTS
G-CSF administration in cadmium-pretreated partially hepatectomized rats restored the suppressed DNA biosynthesis and TK activity (P < 0.001), to levels similar to those found in rats that were partially hepatectomized only. The mitotic index and the percentage of PCNA positive nuclei in hepatocytes were also enhanced in G-CSF administered cadmium-pretreated partially hepatectomized groups of rats.


CONCLUSIONS
The administration of G-CSF triggers events that restore the impaired liver regeneration in this model of reduced hepatocyte proliferation.
Theocharis
S E
SE
Department of Histology and Embryology, School of Medicine, University of Athens, Greece.
Margeli
A P
AP
Goutas
N D
ND
Horti
M G
MG
Karkantaris
C S
CS
Kittas
C N
CN
D000818:Animals; D002104:Cadmium / Q000633:toxicity; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006498:Hepatectomy; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D051381:Rats; D017208:Rats, Wistar
D002104:Cadmium; D016179:Granulocyte Colony-Stimulating Factor