PT  - JOURNAL ARTICLE
AU  - T J Monks
AU  - S S Lau
AU  - R J Highet
TI  - Formation of nontoxic reactive metabolites of p-bromophenol. Identification of a new glutathione conjugate.
DP  - 1984 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 432--437
VI  - 12
IP  - 4
4099  - http://dmd.aspetjournals.org/content/12/4/432.short
4100  - http://dmd.aspetjournals.org/content/12/4/432.full
SO  - Drug Metab Dispos1984 Jul 01; 12
AB  - 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.