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

Lookup NU author(s): Professor Ann DalyORCiD

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Abstract

© 2018 The Royal Society of Chemistry. 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.

Publication metadata

Author(s): Athersuch TJ, Antoine DJ, Boobis AR, Coen M, Daly AK, Possamai L, Nicholson JK, Wilson ID

Publication type: Article

Publication status: Published

Journal: Toxicology Research

Year: 2018

Volume: 7

Issue: 3

Pages: 347-357

Print publication date: 08/05/2018

Online publication date: 06/03/2018

Acceptance date: 07/02/2018

ISSN (print): 2045-452X

ISSN (electronic): 2045-4538

Publisher: Royal Society of Chemistry

URL: https://doi.org/10.1039/c7tx00340d

DOI: 10.1039/c7tx00340d

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