Cholangiocarcinoma and liver cirrhosis in relation to changes due to thioacetamide.

Different doses of thioacetamide (0.05%, 0.1% and 0.15%) were used to induce liver cirrhosis in Wistar rats. Thioacetamide at 0.5% caused cirrhosis by the twelfth week of treatment. A severe bile duct proliferation and cholangiocarcinoma was seen at longer intervals. Animals treated with higher doses (0.1% and 0.15%) of thioacetamide developed more severe intense degenerative changes in the liver and died in the twelfth and eighth week respectively. The serum and tissue contents of Zn and Cu changed in a characteristic fashion that was consistent with the severity of the liver damage. Serum Zn and Cu concentrations were at their lowest in the animals that developed severe degenerative liver and died at higher dose (0.15%) of thioacetamide. This study indicates that treatment of rats with 0.05% thiocetamide is more effective and appropriate for the induction of liver cirrhosis. Continued administration of the drug at this dosage led to the development of further changes in the liver. This model may be suitable for studying these long term changes that occur in the liver and lead to cirrhosis. Events that precede the development of severe bile duct proliferation and cholangiocarcinoma may also be studied.