Rapid Induction of Liver Cirrhosis in Mini Rats by Thioacetamide

Abstract

A histopathological study was carried out on the liver of thioacetamide (TAA)-treated rats of Jcl: Wistar-TgN(ARGHGEN)1Nts strain (Mini rats), in which the expression of growth hormone (GH) gene is suppressed by the presence of antisense transgene, resulting in the reduction of plasma GH levels. Male Wistar (the parental strain of Mini rats) and Mini rats of 4-6 weeks of age were treated with 0.03% TAA in drinking water for up to 8 weeks. The survival rates of Wistar and Mini rats were 91% and 89%, respectively. Plasma alkaline phosphatase activity and total bilirubin concentration in TAA-treated Mini rats increased to a greater extent than those in TAA-treated Wistar rats. Histopathologically, the liver of TAA-treated Mini rats revealed proliferation of ‘atypical’ hepatocytes throughout the course of the experiment. In addition, fibrosis from the periportal area to the centrilobular region associated with oval cell proliferation was observed at 2 weeks. At 8 weeks, cirrhosis accompanied with proliferation of bile duct epithelial cell-like cells was evident. In the liver of Wistar rats, There were only atypical hepatocytes and slight fibrosis without cirrhotic features even at 8 weeks. These results demonstrate a great advantage in the use of Mini rats to produce liver cirrhosis within a short term and suggest some possible relationships between GH deficiency and experimental cirrhogenesis.