Species differences in renal gamma-glutamyl transpeptidase activity do not correlate with susceptibility to 2-bromo-(diglutathion-S-yl)-hydroquinone nephrotoxicity.

Abstract

Administration of 2-bromo-(diglutathion-S-yl)hydroquinone (2-Br-[diGSyl]HQ) (10-30 mumol/kg; i.v.) to rats causes severe renal proximal tubular necrosis. gamma-Glutamyl transpeptidase (gamma-GT) catalyses the first step in the metabolism of glutathione (GSH) and its S-conjugates and the toxicity of 2-Br-(diGSyl)HQ can be emeliorated by inhibition of renal gamma-GT. Species differences in the specific activity of renal gamma-GT have been reported and we now describe the relationship between renal gamma-GT and species differences in susceptibility to 2-Br-(diGSyl)HQ nephrotoxicity. Although rats exhibited the highest specific activity of renal gamma-GT, and were the most sensitive species toward 2-Br-(diGSyl)HQ-mediated nephrotoxicity, renal gamma-GT activity did not correlate with susceptibility in the other species examined. Indeed, the guinea pig, which expressed the lowest activity of renal gamma-GT between the species (8% of the rat) was the only other rodent found to be responsive toward 2-Br-(diGSyl)HQ at the highest dose tested (200 mumol/kg; intracardiac). Thus, factors other than gamma-GT activity probably play an important role in modulating species susceptibility to 2-Br-(diGSyl)HQ nephrotoxicity. Although the reason(s) for the interspecies variation in response to 2-Br-(diGSyl)HQ are unclear at present, it seems possible that differences in both renal biochemistry, such as differences in the relative activities of cysteine conjugate N-acetyl transferase and deacetylase, and renal physiology, contribute to the observed results.

• Authors: S S Lau, T W Jones, R Sioco, B A Hill, R K Pinon, T J Monks
• Journal: Toxicology (Toxicology) Vol. 64 Issue 3 Pg. 291-311 (Dec 03 1990) ISSN: 0300-483X [Print] Ireland
• PMID: 1980038 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hydroquinones
• 2-bromo-(diglutathion-S-yl)hydroquinone
• 2-bromohydroquinone
• gamma-Glutamyltransferase
• Glutathione

Topics

• Animals
• Cricetinae
• Glutathione (analogs & derivatives, toxicity)
• Guinea Pigs
• Hydroquinones (toxicity)
• Kidney Cortex (drug effects, enzymology, pathology, ultrastructure)
• Kidney Diseases (chemically induced)
• Kidney Tubular Necrosis, Acute (chemically induced)
• Male
• Mesocricetus
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Rabbits
• Rats
• Rats, Inbred F344
• Rats, Inbred Strains
• Species Specificity
• gamma-Glutamyltransferase (metabolism)