New Insights into the Acetaminophen Hepatotoxicity Research

Acetaminophen (APAP) toxicity is the leading cause of drug-induced acute liver failure (ALF) in the developed countries; however the underlying mechanisms of APAP toxicity are still not clear. Massive hepatocyte necrosis is the predominant feature of APAP hepatotoxicity; the liver regeneration is the vital process for survival after the toxic insult and many factors can influence liver repair. Emerging evidence shows that inflammation improves liver regeneration during the late phase of APAP hepatotoxicity; enhanced NF-kB activation, an important regulator of inflammation, is associated with improved liver recovery in APAP overdose; some widely used methods are not reliable to reveal liver regeneration in APAP toxicity research. These results indicate that the underlying mechanism of APAP hepatotoxicity is different from what currently well-accepted ones in which, inflammation is frequently considered to be responsible for liver tissue damage, and it is necessary to re-assess the underlying mechanism of liver regeneration in APAP overdose. This manuscript focuses on some new insights into the APAP toxicity research.