Chronological production of thioacetamide-induced cirrhosis in the rat with no mortality.

BACKGROUND: Cirrhotic animal models are useful in studying complications of chronic liver disease. The authors chronologically investigated the effect of thioacetamide (TAA), administered intraperitoneally and adapted individually to weight changes, focusing on the optimal moment to obtain typical features of cirrhosis. MATERIAL AND METHOD: Male Wistar Rats,150-200 g, were intoxicated three times per week with TAA of 200 mg/kg for 4, 8, 12 or 16 weeks (n = 8 per group), respectively and compared with age-matched controls (n = 4 per group). The individual body weight and liver function test were also measured in each group. Liver samples from each group were histologically stained with Sirius red in order to identify the degree of liver fibrosis. RESULTS: Rats intoxicated for 4, 8, 12 or 16 weeks had no mortality and histologically showed hepatitis and advanced fibrosis. At 12 and 16 weeks, all animals showed macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. The weight of the treated groups at different time points was significantly lower than the controls. Routine liver function tests between cirrhotic and control rats showed significantly higher only in alanine transaminase (ALT) and aspartate aminotransferase (AST) at 8 and 12 weeks. However in the cirrhotic rats at 16 weeks, the ALT and AST were much lower than that at 8 and 12 weeks but did not show any difference from the controls. CONCLUSION: Thioacetamide, adapted to individual weight changes, leads to a model of cirrhosis in the rat at 12 and 16 weeks with zero mortality.

Activated Ito cells of cirrhotic liver express M3 muscarinic receptor after thioacetamide exposure.

Ito cells or perisinusoidal stellate cells or hepatic fat storing cells are pericytes of normal liver sinusoidal endothelial cells. Activation of Ito cells by chemicals or toxins causes transdifferentiation into the main collagen-producing cells involving in the progression of liver cirrhosis. Quantitative analysis of Ito cell activation by immunohistochemistry has been shown to be useful in predicting the rate of progression of liver fibrosis in some clinical situations. The present study demonstrated that the activated Ito cells in thioacetamide-induced cirrhotic liver which were immunopositive with alpha smooth muscle actin, expressed M3 muscarinic receptor but not M1, M2, M4 and M5. These findings suggest that the M3 muscarinic receptor might involve in triggering intracellular signalling pathways in activated Ito cell to produce collagen fibers and may be of future interest in hepatic fibrosis therapy.