Comparative role of acetaminophen, carbon tetrachloride and thioacetamide in development of fibrosis in rats.

Abstract

Several hepatotoxicants such as acetaminophen, carbon tetrachloride, and thioacetamide are repeatedly used to develop hepatic fibrosis to mimic the histological and hemodynamic characteristics of human illness. It may be a good idea to establish a better model among these hepatotoxicants to develop hepatic fibrosis. The present study evaluated comparative toxic effects of three model hepatotoxicants for experimental progression of fibrosis or cirrhosis. Acetaminophen (200 mg/kg), carbon tetrachloride (200 µl/kg) and thioacetamide (200 mg/kg) were administered orally, thrice in a week for 8 weeks in different groups. After 8 weeks of exposure, animals were euthanized, blood and tissues were collected for various hematological, serological, tissue biochemical analysis and histological observations for comparative assessment of toxic consequences. Significant deviation was noted in liver function tests, lipid peroxidation, glutathione, activities of superoxide dismutase, catalase, and GSH cycle enzymes; aniline hydroxylase, amidopyrine-N-demethylase, DNA fragmentation and level of hydroxyproline when compared with control group. Histology also depicted damage in liver histoarchitecture with exposure to acetaminophen, carbon tetrachloride and thioacetamide. Tukey's HSD post hoc test confirmed that thioacetamide produced severe toxic effects in comparison to carbon tetrachloride and acetaminophen. In conclusion, toxic effects were noted in ascending order as acetaminophen.