Potentiation of the toxicity of model hepatotoxicants by acetaminophen

Abstract

A 24-hr oral pretreatment of rats with 1.6 g/kg acetaminophen potentiated hepatotoxicity of allyl alcohol, bromobenzene, carbon tetrachloride, 1,1-dichloroethylene, and thioacetamide, as assessed by elevation of serum alanine aminotransferase activity and histopathological examination. Doses, of these hepatotoxicants, which did not cause hepatocellular necrosis, became necrogenic after acetaminophen pretreatment with all toxicants except thioacetamide. Acetaminophen pretreatment did not decrease the threshold dose of toxicity for thioacetamide but did accentuate hepatotoxic doses. Acetaminophen pretreatment potentiated lethality of allyl alcohol and 1,1-dichloroethylene. Upon necropsy, these rats had congested livers and appeared to suffer from hypovolemic shock. We conclude that while acetaminophen was not necrogenic at the doses used in this study, it produced alterations that make hepatocytes much more susceptible to hepatotoxic insult.