OBJECTIVE: The use of modulators of estrogen receptors activation is receiving increasing interest in menopausal medicine. Pure antiestrogens define a group of compounds exhibiting universal antagonistic properties. Nevertheless, we cannot disregard the possibility that they may still have some agonistic actions. Because estradiol (E2) has antioxidant properties, we tested the antioxidant capacity of two pure antiestrogens, ICI 182780 and EM-652 (SCH 57068). DESIGN: The ability of both compounds to protect isolated low-density lipoproteins against copper-induced oxidation in vitro was used as an index of their antioxidant properties. RESULTS: When compared with control (vehicle alone), ICI 182780 and EM-652 significantly increased the lag time of low-density lipoprotein oxidation when present at concentrations of 10 and 0.5 microM or greater, respectively. When compared with estrogens, ICI 182780 was as effective as E2 at the lower concentrations tested (0.1 and 1 microM) but less effective at higher concentrations. EM-652 had similar antioxidant potency as E2 but exerted maximal effects at lower concentration. Combined exposure to E2 and each of the antiestrogens resulted in a higher antioxidant effect than that of antiestrogen alone. Another estrogen (estrone), and selective estrogen-receptor modulators, such as tamoxifen and hydroxytamoxifen, displayed an antioxidant potency that was close to ICI 182780 but lower than EM-652. Progestogens, such as progesterone or medroxyprogesterone acetate, had no antioxidant effect. CONCLUSIONS: Both ICI 182780 and EM-652 exhibited potent antioxidant activity, which could have important biological implications.
OBJECTIVE: The use of modulators of estrogen receptors activation is receiving increasing interest in menopausal medicine. Pure antiestrogens define a group of compounds exhibiting universal antagonistic properties. Nevertheless, we cannot disregard the possibility that they may still have some agonistic actions. Because estradiol (E2) has antioxidant properties, we tested the antioxidant capacity of two pure antiestrogens, ICI 182780 and EM-652 (SCH 57068). DESIGN: The ability of both compounds to protect isolated low-density lipoproteins against copper-induced oxidation in vitro was used as an index of their antioxidant properties. RESULTS: When compared with control (vehicle alone), ICI 182780 and EM-652 significantly increased the lag time of low-density lipoprotein oxidation when present at concentrations of 10 and 0.5 microM or greater, respectively. When compared with estrogens, ICI 182780 was as effective as E2 at the lower concentrations tested (0.1 and 1 microM) but less effective at higher concentrations. EM-652 had similar antioxidant potency as E2 but exerted maximal effects at lower concentration. Combined exposure to E2 and each of the antiestrogens resulted in a higher antioxidant effect than that of antiestrogen alone. Another estrogen (estrone), and selective estrogen-receptor modulators, such as tamoxifen and hydroxytamoxifen, displayed an antioxidant potency that was close to ICI 182780 but lower than EM-652. Progestogens, such as progesterone or medroxyprogesterone acetate, had no antioxidant effect. CONCLUSIONS: Both ICI 182780 and EM-652 exhibited potent antioxidant activity, which could have important biological implications.
Authors: Carole B Rudra; Jean Wactawski-Wende; Kathleen M Hovey; Richard W Browne; Cuilin Zhang; Mary L Hediger; Enrique F Schisterman Journal: Med Sci Sports Exerc Date: 2011-05 Impact factor: 5.411
Authors: MaryFran Sowers; Daniel McConnell; Mary L Jannausch; John F Randolph; Robert Brook; Ellen B Gold; Sybil Crawford; Bill Lasley Journal: Clin Endocrinol (Oxf) Date: 2007-11-02 Impact factor: 3.478
Authors: Susana Novella; Ana Paula Dantas; Gloria Segarra; Pascual Medina; Carlos Hermenegildo Journal: Front Physiol Date: 2012-06-06 Impact factor: 4.566