Jump to main content
Jump to site search

Issue 3, 2018
Previous Article Next Article

Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

Author affiliations

Abstract

After over 60 years of therapeutic use in the UK, paracetamol (acetaminophen, N-acetyl-p-aminophenol, APAP) remains the subject of considerable research into both its mode of action and toxicity. The pharmacological properties of APAP are the focus of some activity, with the role of the metabolite N-arachidonoylaminophenol (AM404) still a topic of debate. However, that the hepatotoxicity of APAP results from the production of the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI/NABQI) that can deplete glutathione, react with cellular macromolecules, and initiate cell death, is now beyond dispute. The disruption of cellular pathways that results from the production of NAPQI provides a source of potential biomarkers of the severity of the damage. Research in this area has provided new diagnostic markers such as the microRNA miR-122 as well as mechanistic biomarkers associated with apoptosis, mitochondrial dysfunction, inflammation and tissue regeneration. Additionally, biomarkers of, and systems biology models for, glutathione depletion have been developed. Furthermore, there have been significant advances in determining the role of both the innate immune system and genetic factors that might predispose individuals to APAP-mediated toxicity. This perspective highlights some of the progress in current APAP-related research.

Graphical abstract: Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

Back to tab navigation

Supplementary files

Publication details

The article was received on 21 Dec 2017, accepted on 07 Feb 2018 and first published on 06 Mar 2018


Article type: Review Article
DOI: 10.1039/C7TX00340D
Citation: Toxicol. Res., 2018,7, 347-357
  •   Request permissions

    Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

    T. J. Athersuch, D. J. Antoine, A. R. Boobis, M. Coen, A. K. Daly, L. Possamai, J. K. Nicholson and I. D. Wilson, Toxicol. Res., 2018, 7, 347
    DOI: 10.1039/C7TX00340D

Search articles by author

Spotlight

Advertisements