Multiple reactive metabolites derived from bromobenzene

Serrine Lau, Terrence Monks, J. R. Gillette

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

It has recently been shown that bromobenzene is converted to multiple reactive metabolites. However, the nature of these reactive metabolites is unclear. In the present manuscript, we have demonstrated that the same cytochromes P-450 activate both bromobenzene and p-bromophenol, and each substrate competitively inhibits the metabolism of the other. Moreover, the covalent binding of p-bromophenol to rat liver microsomes was inhibited by epoxide hydrolase, catechol-O-methyltransferase, superoxide dismutase, glutathione, and ascorbic acid but not by catalase. In contrast, the amount of 4-bromocatechol isolated from microsomal incubations containing p-bromophenol was decreased by glutathione and increased by ascorbic acid and superoxide dismutase. It is thus likely that p-bromophenol is converted to an epoxide that decomposes to 4-bromocatechol and that both the epoxide and the quinone formed from oxidation of 4-bromocatechol may become covalently bound to tissue proteins. However, these chemically reactive metabolites are apparently nontoxic because treatments which increase the covalent binding of p-bromophenol in vitro do not cause toxicity in vivo.

Original languageEnglish (US)
Pages (from-to)291-296
Number of pages6
JournalDrug Metabolism and Disposition
Volume12
Issue number3
StatePublished - 1984
Externally publishedYes

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Metabolites
Epoxy Compounds
Ascorbic Acid
Superoxide Dismutase
Glutathione
Epoxide Hydrolases
Catechol O-Methyltransferase
Manuscripts
Liver Microsomes
Metabolism
Liver
Catalase
Cytochrome P-450 Enzyme System
Toxicity
Rats
4-bromophenol
bromobenzene
Tissue
Oxidation
Substrates

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Multiple reactive metabolites derived from bromobenzene. / Lau, Serrine; Monks, Terrence; Gillette, J. R.

In: Drug Metabolism and Disposition, Vol. 12, No. 3, 1984, p. 291-296.

Research output: Contribution to journalArticle

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