Antioxidant activities of estrogens against aqueous and lipophilic radicals; differences between phenol and catechol estrogens

Natural estrogens have much greater radical-scavenging antioxidant activity than has previously been demonstrated, with activities up to 2.5 times tho se of vitamin C and vitamin E. The biological significance of this finding remains to be elucidated. In this work the antioxidant activity of a range of estrogens (phenolic, catecholic and stilbene-derived) has been studied. The activity of these substances as hydrogen-donating scavengers of free ra dicals in an aqueous solution has been determined by monitoring their relat ive abilities to quench the chromogenic radical cation 2,2'-azinobis-(3-eth ylbenzothiazoline-6-sulphonic acid) (ABTS(.+)). The results show that the o rder of reactivity in scavenging this radical in the aqueous phase is depen dent on the precise estrogenic structure, with phenolic estrogens being mor e potent antioxidants than catecholestrogens or diethylstilbestrol. The abi lity of the same estrogens to scavenge lipid phase radicals has also been a ssessed, determined by the ex vivo enhancement of the resistance of low-den sity lipoprotein (LDL) to oxidation; the order of efficacy is different fro m that in the aqueous phase, with the phenolic estrogens estriol, estrone a nd 17 beta-estradiol being less potent than 2-hydroxyestradiol, 4-hydroxyes tradiol, or diethylstilbestrol. In this lipid-based system, phenolic estrog ens were found to be unable to regenerate cc-tocopherol from LDL subjected to oxidative stress, while at the same time 2- and 4-hydroxyestradiol signi ficantly delayed alpha-tocopherol loss. These results indicate that the var ious estrogens are good scavengers of free radicals generated in both the a queous and the lipophilic phases. The antioxidant activity of an estrogen d epends not only on the hydrophilic or lipophilic nature of the scavenged ra dical, but also on the phenol and catechol structures of the estrogen compo und. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.