Stereoselective formation of bromobenzene glutathione conjugates

Terrence Monks, L. R. Pohl, J. R. Gillette, M. Hong, R. J. Highet, J. A. Ferretti, J. A. Hinson

Research output: Contribution to journalArticle

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Abstract

Two bromobenzene-glutathione conjugates have been detected as both in vivo and in vitro metabolites of bromobenzene. Separation and purification by high pressure liquid chromatography (HPLC) and analysis by 13C and 1H-NMR spectroscopy indicated that the metabolites are trans-3-bromo-6-(glutathion-S-yl)-cyclohexa-2,4-dien-1-ol and trans-4-bromo-6-(glutathion-S-yl)-cyclohexa-2,4-dien-1-ol. The two conjugates are formed in unequal amounts; over a dose range of 25-500 mg/kg the ratio of the two conjugates excreted into bile in 6 h was 1.6 ± 0.1 (mean ± S.E.). Pretreatment of rats with either phenobarbital or 3-methyl-cholanthrene did not significantly alter the ratio of the two conjugates excreted into bile. When bromobenzene was incubated with rat liver microsomes and glutathione, the same two conjugates were formed in the presence but not in the absence of 100 000 × g supernatant. Furthermore, in the presence of 100 000 × g supernatant from control animals, microsomes from rats treated with phenobarbital formed both conjugates 6 times more rapidly than did microsomes from control rats, whereas microsomes from rats treated with 3-methylcholanthrene formed both conjugates less rapidly than did those from control rats. Thus, the data suggest that both conjugates are formed via bromobenzene 3,4-oxide and that their formation requires enzymes in liver cytosol.

Original languageEnglish (US)
Pages (from-to)203-216
Number of pages14
JournalChemico-Biological Interactions
Volume41
Issue number2
DOIs
StatePublished - 1982
Externally publishedYes

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Glutathione
Rats
Rat control
Phenobarbital
Metabolites
Microsomes
Liver
High pressure liquid chromatography
Bile
Methylcholanthrene
Nuclear magnetic resonance spectroscopy
Purification
Animals
Liver Microsomes
Cytosol
bromobenzene
Magnetic Resonance Spectroscopy
Enzymes
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Toxicology

Cite this

Monks, T., Pohl, L. R., Gillette, J. R., Hong, M., Highet, R. J., Ferretti, J. A., & Hinson, J. A. (1982). Stereoselective formation of bromobenzene glutathione conjugates. Chemico-Biological Interactions, 41(2), 203-216. https://doi.org/10.1016/0009-2797(82)90090-4

Stereoselective formation of bromobenzene glutathione conjugates. / Monks, Terrence; Pohl, L. R.; Gillette, J. R.; Hong, M.; Highet, R. J.; Ferretti, J. A.; Hinson, J. A.

In: Chemico-Biological Interactions, Vol. 41, No. 2, 1982, p. 203-216.

Research output: Contribution to journalArticle

Monks, T, Pohl, LR, Gillette, JR, Hong, M, Highet, RJ, Ferretti, JA & Hinson, JA 1982, 'Stereoselective formation of bromobenzene glutathione conjugates', Chemico-Biological Interactions, vol. 41, no. 2, pp. 203-216. https://doi.org/10.1016/0009-2797(82)90090-4
Monks, Terrence ; Pohl, L. R. ; Gillette, J. R. ; Hong, M. ; Highet, R. J. ; Ferretti, J. A. ; Hinson, J. A. / Stereoselective formation of bromobenzene glutathione conjugates. In: Chemico-Biological Interactions. 1982 ; Vol. 41, No. 2. pp. 203-216.
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