Acetaminophen (
APAP) overdose is the major cause of
acute liver failure (ALF) in the Western world. Extensive research is ongoing to identify the mechanisms of
APAP-induced ALF.
APAP-induced acute liver injury is also one of the most commonly studied
drug-induced liver injury models in the field of hepatotoxicity.
APAP toxicity is triphasic and includes three mechanistically interlinked but temporally distinct phases of initiation, progression, and recovery/regeneration. Despite how commonly it is studied, the methods to study
APAP toxicity differ significantly, often leading to confusing and contradictory data. There are number of reviews on mechanisms of
APAP toxicity, but a detailed mechanism-based comprehensive method and list of assays that covers all phases of
APAP hepatotoxicity are missing. The goal of this review is to provide a standard protocol and guidelines to study
APAP toxicity in mice including a test battery that can help investigators to comprehensively analyze
APAP toxicity in the specific context of their hypothesis. Further, we will identify the major roadblocks and common technical problems that can significantly affect the results. This
acetaminophen test battery (ATB) will be an excellent guide for scientists studying this most common and clinically relevant
drug-induced liver injury and will also be helpful as a roadmap for hypothesis development to study novel mechanisms.