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The use of stable isotopes to better define toxic metabolic pathways of p-hydroxyacetanilide (acetaminophen) and p-ethoxyacetanilide (phenacetin)

  • S. D. Nelson
  • W. A. Garland
  • J. R. Mitchell
  • Y. Vaishnev
  • C. N. Statham
  • A. R. Buckpitt

Abstract

Phenacetin (acetophenetidine) is a minor analgesic which has been associated with various toxic effects, including methaemoglobinaemia and haemolysis (Beutler, 1969) and renal damage (Abel, 1970). Phenacetin causes both methaemoglobinaemia and mild hepatic necrosis in hamsters. As with the related analgesic, acetaminophen, phenacetin-induced necrosis is potentiated by 3-methylcholanthrene pretreatment. The severity of necrosis parallels the magnitude of the covalent binding of an arylating metabolite of phenacetin to hepatic proteins and depletion of hepatic glutathione by the formation of a glutathione adduct (Mitchell et al., 1975).

Keywords

Stable Isotope Covalent Binding Hepatic Necrosis Reactive Metabolite Glutathione Depletion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© The Contributors 1978

Authors and Affiliations

  • S. D. Nelson
    • 1
  • W. A. Garland
    • 1
  • J. R. Mitchell
    • 1
  • Y. Vaishnev
    • 1
  • C. N. Statham
    • 1
    • 2
  • A. R. Buckpitt
    • 1
  1. 1.NIH, BethesdaMaryland and Hoffmann-La Roche, Inc.NutleyUSA
  2. 2.Pharmacology-Toxicology Research Associate ProgramNational Institute of General Medical SciencesUSA

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