Glutathione protection against irreversible binding of diethylstilbestrol in the hamster renal cortex.
Hamster renal cortical slices bioactivated the synthetic estrogen, diethylstilbestrol (DES), to reactive metabolites that bound irreversibly to cellular proteins. Incubation of the slices for 30 min at 37 degrees C with 5 mM diethyl maleate prior to the addition of 50 nM [3H]DES for 60 min increased the nonextractable binding of [3H]DES metabolites to cellular protein by 150%, whereas addition of 5 mM glutathione (GSH) decreased the irreversible binding of [3H]DES by 17%. The addition of the 5 mM GSH to the incubation medium caused a 24% increase in tissue nonprotein sulfhydryl (NP-SH) content as estimated by reaction with Ellman's reagent after 30 min at 37 degrees C, while the addition of diethyl maleate for the same time period depleted tissue NP-SH levels by 54%. Kidneys from hamsters treated with the GSH synthesis inhibitor L-buthionine-(S,R)-sulfoximine at a dosage of 1 mmol/kg body wt for 2 hr had 45% of the NP-SH content as compared with kidneys of saline-treated controls. The irreversible binding of [3H]DES metabolites was increased by 60% in renal cortical slices from L-buthionine sulfoximine-treated hamsters. Non-extractable binding of [3H]DES metabolites to renal DNA was not observed. These results suggest that GSH, the predominate NP-SH in the cell, protects against the irreversible binding of DES metabolites to cellular macromolecules.
Department of Biophysics, University of Rochester, School of Medicine and Dentistry, New York 14642.
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Notides
D000818:Animals; D019328:Buthionine Sulfoximine; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000378:metabolism; D008647:Mesocricetus; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000378:metabolism
D008298:Maleates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004054:Diethylstilbestrol; C014476:diethyl maleate; D005978:Glutathione