Inhibition of low-density lipoprotein oxidation by the pure antiestrogens ICI 182780 and EM-652 (SCH 57068).
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).


METHODS
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.
Hermenegildo
Carlos
C
Research Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain.
García-Martínez
María Cinta
MC
Tarín
Juan J
JJ
Cano
Antonio
A
D000975:Antioxidants / Q000494:pharmacology*; D019327:Copper Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D000975:Antioxidants; D004965:Estrogen Antagonists; D008077:Lipoproteins, LDL; D010880:Piperidines; D045167:Progesterone Congeners; D013629:Tamoxifen; D000077267:Fulvestrant; D004970:Estrone; C012121:ritetronium; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D019327:Copper Sulfate