Effect of granulocyte colony-stimulating-factor administration on tissue regeneration due to thioacetamide-induced liver injury in rats.
It has been shown recently that granulocyte colony-stimulating factor (G-CSF) accelerates and enhances the hepatocyte proliferative capacity of partially hepatectomized rats. In the present study, we investigated the effect of G-CSF administration in a rat model of liver injury and regeneration, induced by thioacetamide (TAA) injection. TAA (300 mg/kg body weight) was injected intraperitoneally in male Wistar rats, and this was followed by administration of either saline (group A) or G-CSF at a dose of 150 microg/kg body weight (group B), 24 hr later. The animals were killed at different time points after TAA treatment and the rate of tritiated thymidine incorporation into hepatic DNA, the activity of the enzyme thymidine kinase (EC 2.7.1.21) in the liver, and the assessment of the mitotic index of hepatocytes, were employed to estimate liver regeneration. The administration of TAA caused severe hepatic injury, recognized histopathologically and by the raised activities of the serum hepatic enzymes aspartate and alanine aminotransferases. The hepatic injury, which peaked 36 hr after TAA injection, was followed by a regenerative process of hepatocytes presenting peaks at time points of 48 and 60 hr (group A). The administration of G-CSF 24 hr after the injection of TAA (group B) caused a statistically significantly increase in the hepatocyte proliferation indices examined (P < 0.001), compared to those found in group A at the same time points. It was concluded that G-CSF administration enhanced the hepatocyte proliferative capacity in this model of liver injury induced by TAA administration.
Theocharis
S E
SE
Department of Histology and Embryology, School of Medicine, University of Athens, Greece.
Margeli
A P
AP
Kittas
C N
CN
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000503:physiopathology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008099:Liver / Q000473:pathology / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D013997:Time Factors
D013853:Thioacetamide; D016179:Granulocyte Colony-Stimulating Factor