Protective effect of estrogens and catecholestrogens against peroxidative membrane damagein vitro

The antioxidant effects of natural estrogens (estrone E₁; 17β-estradiol), synthetic estrogens (17α-ethynylestradiol, EE₂; mestranol, MES; diethylstilbestrol, DES) and catechle-strogens (2-hydroxyestradiol; 4-hydroxyestradiol 4-OHE₂) on lipid peroxidation induced by different means in rat liver microsomes were investigated. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances. Prooxidants included Fe³⁺/ADP/reduced NADPH, Fe²⁺/ascorbate,tert-butyl hydroperoxide (t-BOOH) and 2,2′-azobis (2-amidinopropane) (AAPH). Estrogens and catecholestrogens decreased lipid peroxidation in all four systems tested. In the iron/ascorbate model it was shown that (i)-OHE₂ and DES had analogous patterns of inhibition, irrespective of the presence of NADPH or the functional integrity of the microsómes, and (ii) the antioxidant activities of E₁, EE₂ and MES were dependent on the assay conditions with the activity being markedley higher when estrogen metabolism was favored. When peroxidation 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 inhibitory potency with DES and catecholestrogens being the most potent antioxidants under all experimental conditions used. The present results confirm earlier findings and point toward a link between estrogen metabolism and estrogen antioxidant activity. The data also indicate that estrogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-derived species being the most important modes of inhibition.