Comparative Histopathology of Acetaminophen Induced Hepatotoxicity in Animal Models of Mice and Rats

Acetaminophen induced hepatotoxicity is one of the most popular and widely used model for evaluating synthetic and natural compounds that are assumed to have hepatoprotective effects. In this study, the hepatotoxicity of acetaminophen has been investigated in animal models of mice and rats. Liver injury was developed with toxic doses of acetaminophen in fasted mice (500 mg/kg) and rats (800 mg/kg). Hepatotoxicity was assessed after 12 hours of acetaminophen intoxication. In both mice and rats, acetaminophen produced considerable histopathological changes that were manifested as extensive hemorrhage, central vein congestion with endothelium disruption, hydropic degeneration, perivenular necrosis of hepatocytes, microvesicular steatosis and nuclear changes as karyolysis, pyknosis and karyorrhexis. These histopathological changes were more marked and exaggerated in mice compared to rats. The results showed that the extent of hepatic necrosis induced by acetaminophen was more severe in mice while rats appeared to be relatively resistant. These inter-species differences in susceptibility of acetaminophen induced hepatotoxicity supports the use of mice as an appropriate and clinically relevant hepatotoxic animal model for testing hepatoprotective agents and to investigate mechanisms of their therapeutic action.