2-Hydroxy-4-glutathion-S-yl-17β-estradiol and 2-hydroxy-1-glutathion-S-yl-17β-estradiol produce oxidative stress and renal toxicity in an animal model of 17β-estradiol-mediated nephrocarcinogenicity

Michael Butterworth, Serrine Lau, Terrence Monks

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Chronic exposure of male Syrian hamsters to a variety of estrogens has been linked with a high incidence of renal carcinoma. The basis of this species and tissue specificity remains to be resolved. We have recently shown that (i) 17β-estradiol is nephrotoxic in the hamster in a manner dependent upon the activity of γ-glutamyl transpeptidase and (ii) 17β-estradiol is metabolized to a variety of catechol estrogen glutathione conjugates. We report that the catechol estrogen glutathione conjugates exhibit redox properties similar to those of the catechol estrogens, and maintain the ability to generate superoxide radicals. Administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol or 2-hydroxy-1-glutathion-S-yl-17β-estradiol (0.27-5.0 μmol/kg) to Syrian hamsters, produces mild nephrotoxicity. Repeated daily administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol causes a sustained elevation in urinary markers of renal damage and in the concentration of renal protein carbonyls and lipid hydroperoxides. Catechol estrogen oxidation and conjugation of glutathione in the liver, followed by the selective uptake of the redox active conjugates in tissues rich in γ-glutamyl transpeptidase may contribute to 17β-estradiol-induced renal tumors in the hamster.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalCarcinogenesis
Volume19
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

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Catechol Estrogens
Glutathione
Estradiol
Oxidative Stress
Animal Models
Kidney
gamma-Glutamyltransferase
Mesocricetus
Cricetinae
Oxidation-Reduction
Species Specificity
Organ Specificity
Lipid Peroxides
Superoxides
Estrogens
Carcinoma
Liver
Incidence
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

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title = "2-Hydroxy-4-glutathion-S-yl-17β-estradiol and 2-hydroxy-1-glutathion-S-yl-17β-estradiol produce oxidative stress and renal toxicity in an animal model of 17β-estradiol-mediated nephrocarcinogenicity",
abstract = "Chronic exposure of male Syrian hamsters to a variety of estrogens has been linked with a high incidence of renal carcinoma. The basis of this species and tissue specificity remains to be resolved. We have recently shown that (i) 17β-estradiol is nephrotoxic in the hamster in a manner dependent upon the activity of γ-glutamyl transpeptidase and (ii) 17β-estradiol is metabolized to a variety of catechol estrogen glutathione conjugates. We report that the catechol estrogen glutathione conjugates exhibit redox properties similar to those of the catechol estrogens, and maintain the ability to generate superoxide radicals. Administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol or 2-hydroxy-1-glutathion-S-yl-17β-estradiol (0.27-5.0 μmol/kg) to Syrian hamsters, produces mild nephrotoxicity. Repeated daily administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol causes a sustained elevation in urinary markers of renal damage and in the concentration of renal protein carbonyls and lipid hydroperoxides. Catechol estrogen oxidation and conjugation of glutathione in the liver, followed by the selective uptake of the redox active conjugates in tissues rich in γ-glutamyl transpeptidase may contribute to 17β-estradiol-induced renal tumors in the hamster.",
author = "Michael Butterworth and Serrine Lau and Terrence Monks",
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T1 - 2-Hydroxy-4-glutathion-S-yl-17β-estradiol and 2-hydroxy-1-glutathion-S-yl-17β-estradiol produce oxidative stress and renal toxicity in an animal model of 17β-estradiol-mediated nephrocarcinogenicity

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AU - Lau, Serrine

AU - Monks, Terrence

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N2 - Chronic exposure of male Syrian hamsters to a variety of estrogens has been linked with a high incidence of renal carcinoma. The basis of this species and tissue specificity remains to be resolved. We have recently shown that (i) 17β-estradiol is nephrotoxic in the hamster in a manner dependent upon the activity of γ-glutamyl transpeptidase and (ii) 17β-estradiol is metabolized to a variety of catechol estrogen glutathione conjugates. We report that the catechol estrogen glutathione conjugates exhibit redox properties similar to those of the catechol estrogens, and maintain the ability to generate superoxide radicals. Administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol or 2-hydroxy-1-glutathion-S-yl-17β-estradiol (0.27-5.0 μmol/kg) to Syrian hamsters, produces mild nephrotoxicity. Repeated daily administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol causes a sustained elevation in urinary markers of renal damage and in the concentration of renal protein carbonyls and lipid hydroperoxides. Catechol estrogen oxidation and conjugation of glutathione in the liver, followed by the selective uptake of the redox active conjugates in tissues rich in γ-glutamyl transpeptidase may contribute to 17β-estradiol-induced renal tumors in the hamster.

AB - Chronic exposure of male Syrian hamsters to a variety of estrogens has been linked with a high incidence of renal carcinoma. The basis of this species and tissue specificity remains to be resolved. We have recently shown that (i) 17β-estradiol is nephrotoxic in the hamster in a manner dependent upon the activity of γ-glutamyl transpeptidase and (ii) 17β-estradiol is metabolized to a variety of catechol estrogen glutathione conjugates. We report that the catechol estrogen glutathione conjugates exhibit redox properties similar to those of the catechol estrogens, and maintain the ability to generate superoxide radicals. Administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol or 2-hydroxy-1-glutathion-S-yl-17β-estradiol (0.27-5.0 μmol/kg) to Syrian hamsters, produces mild nephrotoxicity. Repeated daily administration of 2-hydroxy-4-glutathion-S-yl-17β-estradiol causes a sustained elevation in urinary markers of renal damage and in the concentration of renal protein carbonyls and lipid hydroperoxides. Catechol estrogen oxidation and conjugation of glutathione in the liver, followed by the selective uptake of the redox active conjugates in tissues rich in γ-glutamyl transpeptidase may contribute to 17β-estradiol-induced renal tumors in the hamster.

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