A/J mice are more susceptible than C57BL/6 to acetaminophen-induced hepatotoxicity

Abstract

Acetaminophen (APAP) is commonly used to treat fever and pain. However, when in overdose is the predominant cause of hepatotoxicity. Despite advances in understanding the mechanisms of APAP-induced hepatotoxicity, the management of acute liver failure remains a challenge. Thus, more relevant experimental models are crucial to provide a better understanding of this condition. The aim of this study is to evaluate the effect of APAP-induced hepatotoxicity on A/J mice using C57BL/6 as reference experimental model. Eight- to ten-week-old male A/J and C57BL/6 mice were treated with APAP (300 or 500 mg/kg) by intraperitoneal injection. After 24 h total blood leukocyte counting, plasma levels of alanine amino transferase (ALT) and aspartate amino transferase (AST), histopathological analysis of liver, lung and kidney were evaluated. A/J mice presented reduction in circulating leukocytes concomitant with the increase in plasma levels of ALT and AST, and liver necrosis when treated with 300 and 500 mg/kg of APAP. C57BL/6 mice presented similar results only with 500 mg/kg of APAP. Our results show that A/J mice have a marked susceptibility to the effects of APAP and could be considered as an experimental model to study APAP-induced toxicity.