Lookup NU author(s): Professor Ann Daly
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© 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.
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
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
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