ESTRADIOL-INDUCED EFFECTS ON GLUTATHIONE METABOLISM IN RAT HEPATOCYTES

Glutathione plays an important role in the intracellular protection ag ainst oxidative stress and damage in the liver. It is generally assume d that the toxic potential of estrogens is linked to reactive metaboli tes generated during their enzymatic oxidation in hepatic microsomes. In the present study, the effects of pharmacological doses of estradio l on glutathione metabolism using isolated rat hepatocytes are describ ed. Estradiol (0.1-1.5 mM) produced a dose-dependent depletion of cell ular reduced glutathione (GSH), whereas it did not alter the glutathio ne disulfide (GSSG) excretion into the medium. The viability of cells exposed to the estrogen did not change even when conditions of exacerb ated toxicity (addition of either 1 mM diethylmaleimide or 30 muM dico umarol) were used. In addition, estradiol was shown to exert protectiv e effects against the spontaneous lipid peroxidation in liver cells. I n rat liver microsomes, estradiol (5-50 muM) significantly interacted with GSH only when an NADPH-regenerating system was incorporated into the medium.