Glutathione conjugates of 2-bromohydroquinone are nephrotoxic.

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 gamma-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 in part to 2-bromohydroquinone GSH conjugates formed in the liver and subsequently transported to the kidney and converted to ultimate nephrotoxic metabolite(s).

• Authors: T J Monks, S S Lau, R J Highet, J R Gillette
• Journal: Drug metabolism and disposition: the biological fate of chemicals (Drug Metab Dispos) 1985 Sep-Oct Vol. 13 Issue 5 Pg. 553-9 ISSN: 0090-9556 [Print] United States
• PMID: 2865102 (Publication Type: Journal Article)

Chemical References

• Hydroquinones
• Phenols
• 2-bromohydroquinone
• 2-bromophenol
• gamma-Glutamyltransferase
• Glutathione
• Cysteine

Topics

• Animals
• Cysteine (metabolism)
• Glutathione (metabolism)
• Hydroquinones (metabolism)
• Kidney (drug effects)
• Magnetic Resonance Spectroscopy
• Male
• Microsomes, Liver (metabolism)
• Phenols (metabolism)
• Rats
• Rats, Inbred Strains
• gamma-Glutamyltransferase (physiology)