Metabolites of acetaminophen trigger Ca2+ release from liver microsomes

Detcho A. Stoyanovsky, Arthur I. Cederbaum

    Research output: Contribution to journalArticlepeer-review

    12 Scopus citations

    Abstract

    Release of mitochondrial calcium is believed to play a key role in the toxicity of acetaminophen in biological systems. Elevated cytosolic Ca2+ may also result from activation of calcium releasing channels. The major metabolites of acetaminophen, benzoquinone imine and 1,4-benzoquinone, induced Ca2+ release in isolated rat liver microsomes. The 1,4-benzoquinone-induced release of calcium was suppressed by ryanodine and fully inhibited by reduced glutathione. Concentrations of 1,4-benzoquinone that induced Ca2+ release did not affect the activity of the microsomal Ca2+, Mg2+-APTase. The binding of [3H]ryanodine to liver microsomes, however, was significantly decreased by 1,4-benzoquinone, suggesting a direct interaction of this metabolite with the ryanodine-binding protein (ryanodine receptor). These results suggest that cellular Ca2+ levels may be elevated by acetaminophen by pathways involving, in part, activation of Ca2+ releasing channels such as the ryanodine receptor. Copyright (C) 1999 Elsevier Science Ireland Ltd.

    Original languageEnglish
    Pages (from-to)23-29
    Number of pages7
    JournalToxicology Letters
    Volume106
    Issue number1
    DOIs
    StatePublished - 20 May 1999

    Keywords

    • Acetaminophen
    • Ca-release
    • Liver microsomes
    • Metabolites

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