Al-Bader A, Mathew T C, Abul H, Al-Sayer H, Singal P K, Dashti H M
Department of Pathology, Faculty of Allied Health Sciences and Nursing, Kuwait University Health Sciences Center, Safat.
Mol Cell Biochem. 2000 May;208(1-2):1-10. doi: 10.1023/a:1007082515548.
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.
使用不同剂量的硫代乙酰胺（0.05%、0.1%和0.15%）诱导Wistar大鼠肝硬化。0.5%的硫代乙酰胺在治疗第12周时导致肝硬化。较长时间后可见严重的胆管增生和胆管癌。用较高剂量（0.1%和0.15%）硫代乙酰胺治疗的动物肝脏出现更严重的强烈退行性变化，分别在第12周和第8周死亡。锌和铜的血清及组织含量呈特征性变化，与肝损伤的严重程度一致。在出现严重肝脏退行性变并因高剂量（0.15%）硫代乙酰胺死亡的动物中，血清锌和铜浓度最低。本研究表明，用0.05%硫代乙酰胺治疗大鼠对诱导肝硬化更有效且合适。以该剂量持续给药会导致肝脏出现进一步变化。该模型可能适合研究肝脏中发生的导致肝硬化的这些长期变化。也可以研究严重胆管增生和胆管癌发生之前的事件。
