Phenobarbital in comparison with carbon tetrachloride and phenobarbital-induced cirrhosis in rat liver regeneration

Background. The simultaneous administration of carbon tetrachloride (CCl4) and phenobarbital in the rat produces one of the most common experimental models of liver cirrhosis. As phenobarbital also has a hepatotrophic effect, its role in liver regeneration following partial hepatectomy (HTX) is not elucidated. Purpose. To examine the effect of long-term administration of phenobarbital in liver regeneration after HTX with regard to CCl4-induced cirrhotic rat model. Materials and Methods. The liver regeneration following HTX in phenobarbital-treated rats (PB rats) was compared to that seen in cirrhotic rats (LC rats), induced by oral gavage of CCl4 and phenobarbital, and normal rats. The effect of the withdrawal of phenobarbital was also examined. Liver regeneration was estimated 24 h after the HTX by measuring the liver weight, the DNA content in the liver, and [H-3]thymidine incorporation into the DNA. Results. Treatment with CCl4 and phenobarbital caused liver deformity, and the highest percentage of liver weight regeneration was seen in LC rats with this deformity, even though [H-3]thymidine incorporation into the DNA was impaired in this group. Phenobarbital had a hepatotrophic effect, but its withdrawal caused a decrease in liver mass and cessation of body weight gain. The change in the DNA content 24 h after HTX was negative in PB rats. Conclusions. Liver regeneration could not be estimated using liver or body weight in the PB or LC rat model. [H-3]Thymidine incorporation into the DNA was reliable indicator of liver regeneration in the different liver states during the early stage after HTX. Although the DNA content with respect to total liver mass was obscured due to liver inflation in PB rats, [H-3]thymidine incorporation into the DNA between PB rats and normal rats was similar. (C) 1999 Academic Press.