FORMATION OF NONTOXIC REACTIVE METABOLITES OF PARA-BROMOPHENOL - IDENTIFICATION OF A NEW GLUTATHIONE CONJUGATE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (4) , 432-437
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. 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 (i.e. phenobarbital treatment and the absence of glutathione) did not cause toxicity in vivo. Chemically reactive metabolite(s) of p-bromophenol evidently do not play a role in bromobenzene-mediated hepatotoxicity.