A standard hepatotoxic model produced by paracetamol in rat

Oral administration of paracetamol in graded doses (250, 500 and 1000 mg/kg, once orally) damaged the liver of rats after 48 hrs, and the severity and extent of liver damage appeared to be dose dependent. At histopathological examination, the hepatic lobules revealed congestion, degeneration and focal necrosis. The hepatocytes appeared large, vacuolated with small condensed pyknotic nuclei. Cytolysis, karyolysis and karyorrhexis of many hepatocytes showing vacuolar degeneration or with eosinophilic cytoplasm were observed. The zonal location of hepatic necrosis was mid to centrilobular. Based on the overview of the liver damage caused by different doses of paracetamol in rats, it has been concluded that paracetamol produces standard and uniform hepatic damage at a single oral dose of 500 mg/kg body weight. It suggests that paracetamol at this dose may produce a standard hepatotoxic model for experimental toxicology.