PROTECTIVE EFFECT OF ESTROGENS AND CATECHOLESTROGENS AGAINST PEROXIDATIVE MEMBRANE DAMAGE IN-VITRO

The antioxidant effects of natural estrogens (estrone, E(1); 17 beta-e stradiol), synthetic estrogens (17 alpha-ethynylestradiol, EE(2); mest ranol, MES; diethylstilbestrol, DES) and catecholestrogens (2-hydroxye stradiol; 4-hydroxyestradiol, 4-OHE) on 2 lipid peroxidation induced b y different means in rat liver microsomes were investigated. The exten t of lipid peroxidation was determined by measuring thiobarbituric aci d reactive substances. Prooxidants included Fe3+/ADP/reduced NADPH, Fe 2+/ascorbate, tert-butyl hydroperoxide (t-BOOH) and 2,2'azobis(2-amidi nopropane) (AAPH). Estrogens and catecholestrogens decreased lipid per oxidation in all four systems tested. In the iron/ascorbate model it w as shown that (i) 4-OHE(2) and DES had analogous patterns of inhibitio n, irrespective of the presence of NADPH or the functional integrity o f the microsomes, and (ii) the antioxidant activities of E(1), EE(2) a nd MES were dependent on the assay conditions with the activity being markedly higher when estrogen metabolism was favored. When peroxidatio n was initiated by the peroxyl radical generator AAPH, the inhibitory effects observed were least pronounced. Our data also showed that, in each of the systems, all inhibitors displayed the same order of inhibi tory potency with DES and catecholestrogens being the most potent anti oxidants under all experimental conditions used. The present results c onfirm earlier findings and point toward a link between estrogen metab olism and estrogen antioxidant activity. The data also indicate that e strogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-der ived species being the most important modes of inhibition.