Title: Glutathione protection against irreversible binding of diethylstilbestrol in the hamster renal cortex.

Authors: Adams, S P; Notides, A C

Published In Fundam Appl Toxicol, (1987 Nov)

Abstract: 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.

PubMed ID: 3692026

MeSH Terms: No MeSH terms associated with this publication