Co-oxidation of 2-bromohydroquinone by renal prostaglandin synthase. Modulation of prostaglandin synthesis by 2-bromohydroquinone and glutathione

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Abstract

Homogenates from rat renal papillae, a rich source of the prostaglandin (PH) H synthase system (PHS), metabolized (14C]2-bromohydroquinone, in the presence of arachidonic acid, to products which are covalently bound to protein. The co-oxidation of 2-bromohydroquinone caused a concentration-dependent stimulation in 6-keto-PGF(1α), thromboxane B2, PGF(2α), PGE(2), and PGD2 formation. Glutathione (1 mM) caused a decrease in prostaglandin formation and inhibited the arachidonic acid-supported covalent binding of [14C]2-bromohydroquinone with the concomitant formation of [14C]2-bromohydroquinone-glutathione conjugates, oxidized glutathione, and an increase in the recovery of [14C]2-bromohydroquinone. NADPH also inhibited [14C]2-bromohydroquinone covalent binding, probably by reduction of the semiquinone radical back to the hydroquinone. Indomethacin and aspirin, inhibitors of the cyclooxygenase component of PHS, and propylthiouracil and methimazole, inhibitors of the hydroperoxidase component of PHS, inhibited the arachidonic acid-supported covalent binding of [14C]2-bromohydroquinone by 94%, 52%, 78%, and 79% respectively. These data suggest that 1) renal PHS may play a role in activating the nephrotoxin, 2-bromohydroquinone, and that 2) xenobiotic metabolism and its subsequent effects on glutathione levels can modulate renal prostaglandin synthesis.

Original languageEnglish (US)
Pages (from-to)801-807
Number of pages7
JournalDrug Metabolism and Disposition
Volume15
Issue number6
StatePublished - Dec 1 1987

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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