Varying effects of sulfhydryl nucleophiles on acetaminophen oxidation and sulfhydryl adduct formation

Alan R Buckpitt, Douglas E. Rollins, Jerry R. Mitchell

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The effects of glutathione, cysteine, N-acetylcysteine, cysteamine, α-mercaptopropionylglycine and methionine on the NADPH-dependent metabolism and covalent binding of acetaminophen have been examined in mouse liver microsomal incubations. With the exception of methionine, all of the nucleophiles decreased covalent binding by forming adducts with the electrophilic metabolite of acetaminophen. The adducts were measured quantitatively by high pressure liquid chromatography. In contrast to glutathione, N-acetylcysteine and α-mercaptopropionylglycine, both cysteamine and cysteine in high concentrations also decreased covalent binding of acetaminophen through another mechanism, inhibition of the formation of the reactive acetaminophen metabolite. These results indicate that both inhibition of metabolite formation and detoxification of metabolite by sulfhydryl adduct formation are mechanisms that can be important in reducing acetaminophen toxicity in overdosed patients treated with these nucleophiles.

Original languageEnglish (US)
Pages (from-to)2941-2946
Number of pages6
JournalBiochemical Pharmacology
Volume28
Issue number19
DOIs
StatePublished - Oct 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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