Formation of nontoxic reactive metabolites of p-bromophenol. Identification of a new glutathione conjugate

T. J. Monks, S. S. Lau, R. J. Highet

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

A microsomal metabolite of p-bromophenol was isolated and identified as 6-(glutathion-S-yl)-4-bromocatechol. p-Bromophenol is metabolized in rat liver microsomes in part to 4-bromocatechol. The catechol undergoes autooxidation to the corresponding quinone or semiquinone, which can either covalently bind to microsomal protein or, in the presence of glutathione, form a glutathione conjugate. Superoxide dismutase inhibited these reactions by preventing the superoxide anion-mediated oxidation of 4-bromocatechol. Thus, in the presence of glutathione, superoxide dismutase caused a decrease in conjugate formation with a corresponding increase in 4-bromocatechol levels. Conditions which increased the in vitro covalent binding of p-bromophenol (namely, phenobarbital treatment and the absence of glutathione) did not cause toxicity in vivo. Thus, chemically reactive metabolite(s) of p-bromophenol do not play a role in bromobenzene-mediated hepatotoxicity.

Original languageEnglish (US)
Pages (from-to)432-437
Number of pages6
JournalDrug Metabolism and Disposition
Volume12
Issue number4
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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