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N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen.
Results of partitioning experiments indicate that N-acetyl-p-benzoquinone imine is a major metabolite of acetaminophen, a considerable fraction of which is rapidly reduced back toacetaminophen.
Molecular mechanisms of the hepatotoxicity caused by acetaminophen.
  • S. Nelson
  • Chemistry, Medicine
    Seminars in liver disease
  • 1 November 1990
Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis.
The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in
Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4.
It is indicated that CYP3A4, the major P450 isoform in human liver and enterocytes, contributes appreciably to the formation of the cytotoxic metabolite NAPQI at therapeutically relevant concentrations of APAP and suggest that APAP may be a previously unrecognized inhibitor of this enzyme.
Mechanisms of N-acetyl-p-benzoquinone imine cytotoxicity.
The toxicity of NAPQI to isolated hepatocytes may result primarily from its oxidative effects on cellular proteins, especially in cells pretreated with BCNU or diethylmaleate.
Managing the challenge of chemically reactive metabolites in drug development
An assessment of the current approaches used for the evaluation of chemically reactive metabolites and how these approaches are being used within the pharmaceutical industry to assess and minimize the potential of drug candidates to cause toxicity is presented.
Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6.
Although at toxic doses of APAP P 450 2E1 is the more efficient catalyst for the formation of the toxic metabolite NAPQI, P450 2A6 also can contribute significantly to NAPZI production.
The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran.
Investigation with (R)-(+)-pulegone-d6 and 18O2 strongly indicate that menthofuran is formed by a sequence of reactions that involve: 1) oxidation of an allylic methyl group, 2) intramolecular cyclization to form a hemiketal, and 3) dehydration to form the furan.