Glutathione conjugates of 2-bromohydroquinone are nephrotoxic

Terrence Monks, Serrine Lau, R. J. Highet, J. R. Gillette

Research output: Contribution to journalArticle

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Abstract

Incubation of either o-bromophenol or 2-bromohydroquinone with rat liver microsomes and 0.25 mM 35S-glutathione (GSH) gave rise to several isomeric 35S-GSH conjugates. A mixture of these isomeric GSH conjugates was prepared chemically and two were purified by HPLC; 1H-NMR spectroscopy revealed that one was 2-bromo-3-(glutathion-S-yl)hydroquinone and the other was a disubstituted GSH conjugate which could be either 2-bromo-3,5-(diglutathion-S-yl)hydroquinone or 2-bromo-3,6-(diglutathion-S-yl)hydroquinone. Injection of the disubstituted GSH conjugate intravenously to rats caused substantial elevations in blood urea nitrogen levels. Treatment of rats with AT-125 (Acivicin; NSC 163501; 10 mg/kg ip) caused a substantial inhibition of kidney γ-glutamyl transpeptidase activity and decreased 2-bromohydroquinone-mediated elevations in blood urea nitrogen. These findings are consistent with the view that the kidney necrosis observed after administration of either bromobenzene (1), o-bromophenol (2), or 2-bromohydroquinone (3) might be due to part of 2-bromohydroquinone GSH conjugates formed in the liver and subsequently transported to the kidney and converted to ultimate nephrotoxic metabolite(s).

Original languageEnglish (US)
Pages (from-to)553-559
Number of pages7
JournalDrug Metabolism and Disposition
Volume13
Issue number5
StatePublished - 1985
Externally publishedYes

Fingerprint

acivicin
Glutathione
Rats
Blood Urea Nitrogen
Kidney
Liver
Urea
Blood
Nitrogen
gamma-Glutamyltransferase
Liver Microsomes
Metabolites
Nuclear magnetic resonance spectroscopy
Necrosis
Magnetic Resonance Spectroscopy
High Pressure Liquid Chromatography
Injections
2-bromohydroquinone

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Glutathione conjugates of 2-bromohydroquinone are nephrotoxic. / Monks, Terrence; Lau, Serrine; Highet, R. J.; Gillette, J. R.

In: Drug Metabolism and Disposition, Vol. 13, No. 5, 1985, p. 553-559.

Research output: Contribution to journalArticle

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