NQO2 is a reactive oxygen species generating off-target for acetaminophen

Teemu P. Miettinen (Lead / Corresponding author), Mikael Björklund

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)
    184 Downloads (Pure)

    Abstract

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity.

    Original languageEnglish
    Pages (from-to)4395-4404
    Number of pages10
    JournalMolecular Pharmaceutics
    Volume11
    Issue number12
    Early online date14 Oct 2014
    DOIs
    Publication statusPublished - 1 Dec 2014

    Keywords

    • acetaminophen
    • CETSA
    • drug target
    • NQO2
    • paracetamol
    • quinone reductase 2
    • superoxide

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