Glutathione depletion in human erythrocytes and rat liver: a study on the interplay between bioactivation and inactivation functions of liver and blood

Toxicology in Vitro : an International Journal Published in Association with BIBRA
N G Palmen, C T Evelo

Abstract

The interplay between bioactivation and inactivation functions of human erythrocytes and rat liver was studied. Glutathione depletion was used as a measure of the amount of reduced glutathione (GSH)-reactive compound. Iodoacetamide (IAcA), N-ethylmaleimide (NEM) and diethyl maleate (DEM), which are electrophiles that need no metabolic activation, were able to deplete GSH in incubations with either aqueous GSH solution or erythrocytes. These results indicate that these compounds can pass the erythrocyte membrane. Cyclophosphamide (CP), 3-hydroxyacetanilide (3-HAA) and 2-methylfurane (2-MF) needed metabolic activation by rat liver microsomes to deplete glutathione in incubations with aqueous GSH solution or erythrocytes. By measuring the sum of both reduced and oxidized glutathione [ = total glutathione (GT)] it became clear that GSH-reactive metabolites are generated out of CP, 3-HAA and 2-MF by the action of microsomes and that these metabolites can pass through the erythrocyte membrane. As GT depletion was higher when microsomes of phenobarbital-pretreated rats were used, the metabolites were (are expected to be) generated by phenobarbital-inducible enzymes. GT was also depleted in incubations with haemolysate and 3-HAA or 2-M...Continue Reading

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Citations

Mar 1, 2011·Air Quality, Atmosphere, & Health·Ralph J DelfinoNosratola D Vaziri
Jan 1, 2012·Dose-response : a Publication of International Hormesis Society·Idolo TedescoGian Luigi Russo
Oct 25, 2017·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Heather Wallace
Nov 7, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simone StegmüllerElke Richling

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