Effects of granulocyte colony stimulating-factor in a rat model of acute liver injury.
OBJECTIVE
Controversial experimental observations suggest that granulocyte colony stimulating-factor may promote hepatic regeneration after hepatectomy and chemical injury either by directly stimulating adult liver cells or facilitating the mobilization of bone marrow cells and their homing to the liver. We investigated whether different schedules of granulocyte colony stimulating-factor administration protect against experimental acute liver injury.


METHODS
Acute liver injury was induced in Sprague-Dawley fed rats by injecting a single intraperitoneal dose of carbon tetrachloride. Recombinant human granulocyte colony stimulating-factor or vehicle was given daily after intoxication (4 days) or before (7 days) and after carbon tetrachloride administration. Liver injury and regeneration were assessed 2 and 4 days after damage. Bone marrow cells mobilization was evaluated by the white blood cell count and the assessment of circulating clonogenic haematopoietic progenitors (colony forming unit-cells).


RESULTS
In this experimental model, although granulocyte colony stimulating-factor induced the significant mobilization of colony forming unit-cells, the study cytokine had no effect on liver injury (serum alanine amino transaminase level and necrotic index) and liver regeneration (mitotic index and bromodeoxyuridine incorporation), regardless of the administration schedule.


CONCLUSIONS
This study does not support the conclusion that: (1) granulocyte colony stimulating-factor exerts a protective effect against toxic-induced, non-lethal acute liver injury and (2) promotes hepatocyte regeneration.
Caraceni
P
P
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, and Ospedale Policlinico S. Orsola-Malpighi, Bologna, Italy. paolo.caraceni@unibo.it
Giannone
F
F
Catani
L
L
Talarico
S
S
Pertosa
A M
AM
Domenicali
M
M
Fogli
M
M
Principe
A
A
Trevisani
F
F
Baccarani
M
M
Bernardi
M
M
Lemoli
R M
RM
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019044:Image Cytometry; D007150:Immunohistochemistry; D007958:Leukocyte Count; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D016896:Treatment Outcome
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D002251:Carbon Tetrachloride