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-CS F) accelerates and enhances the hepatocyte proliferative capacity of partia lly hepatectomized rats. In the present study, we investigated the effect o f G-CSF administration in a rat model of liver injury and regeneration, ind uced by thioacetamide (TAA) injection. TAA (300 mg/kg body weight) was inje cted intraperitoneally in male Wistar rats, and this was followed by admini stration of either saline (group A) or G-CSF at a dose of 150 mu g/kg body weight (group B), 24 hr later. The animals were killed at different time po ints 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 act ivities of the serum hepatic enzymes aspartate and alanine aminotransferase s. The hepatic injury, which peaked 36 hr after TAA injection, was followed by a regenerative process of hepatocytes presenting peaks at time points o f 48 and 60 hr (group A). The administration of G-CSF 24 hr after the injec tion of TAA (group B) caused a statistically significantly increase in the hepatocyte proliferation indices examined (P < 0.001), compared to those fo und in groupA at the same time points. It was concluded that G-CSF administ ration enhanced the hepatocyte proliferative capacity in this model of live r injury induced by TAA administration.