CYTOPROTECTIVE ACTIONS OF ESTROGENS AGAINST TERT-BUTYL HYDROPEROXIDE-INDUCED TOXICITY IN HEPATOCYTES

Estrogens are effective antioxidants in diverse biological systems. De spite their antioxidant activities, it is not known yet whether estrog ens prevent or alleviate liver toxicity induced by oxidative stress. I n the present work, we studied this possibility by examining in vitro the protective potential of different estrogen compounds (17 beta-estr adiol, 2-hydroxyestradiol, and -diethylstilbestrol) against tert-butyl hydroperoxide-induced hepatocyte damage. Various parameters such as c ell viability, lipid peroxidation, adenine nucleotide content, and thi ol status were measured as an index of cytotoxicity. The protective ef fects of estrogens were compared to those of the iron chelator deferox amine. The molecules tested prevented oxidant-induced cell death diffe rently, showing variable degrees of protection. Deferoxamine was the m ost potent agent, followed by diethylstilbestrol and 2-hydroxyestradio l, 17 beta-estradiol being the least efficient. The inhibitory effects on lipid and thiol oxidations paralleled the effects on cell viabilit y. The molecules also reduced the oxidant-induced ATP depletion, excep t for 17 beta-estradiol which had no effect an the decreased ATP level s. Our results suggest that the mechanisms of the preventive actions o f estrogens may be related not only to their antioxidant activity agai nst free radicals, but also and to a lesser extent to the maintenance of the normal redox status of the cell, which partially recovers the i ntracellular GSH levels. BIOCHEM PHARMACOL 56;11:1463-1469, 1998. (C) 1998 Elsevier Science Inc.