In vitro pro- and antioxidant properties of estrogens.
The pro- and antioxidant properties of estrogens are subject of debate. The apparent discrepancy is largely caused by the chemical heterogeneity in the estrogen family and by their concentration and the environment in which they are found. To gain some insight into this debate, we determined whether estradiol (E(2)), estrone (E(1)), the 2-, 4- and 16alpha-hydroxyestrogens and also the 2- and 4-methoxyestrogens are: (1) good electron-donors; (2) capable of O(2) consumption and DNA strand break induction; (3) capable of inhibiting lipid peroxidation in vitro. E(2), E(1) and 16alpha-hydroxyestrone (16alpha-OHE(1)) were not pro-oxidants and were rather weak antioxidants, while the 2- and 4-hydroxyestrogens demonstrated both properties inducing DNA strand breaks damage as well as inhibiting lipid peroxidation. The 4-hydroxyestrogens consumed O(2) and induced DNA strand breaks to a level approximately 2.5-fold higher than the 2-hydroxyestrogens, but these hydroxyestrogens exhibited similar antioxidant capacity, as measured by inhibition of lipid peroxidation. The 4-methoxyestrogens cannot induce oxidative damage to DNA but can inhibit lipid peroxidation, although being less potent than the 2-methoxyestrogens and the 2- and 4-hydroxyestrogens. The 2-methoxyestrogens were both potent electron donors and inhibitors of lipid peroxidation. Although 2-methoxyestrogens cannot generate superoxide in vitro, they may also be considered pro-oxidants in vivo.
Thibodeau
Paul A
PA
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Université de Sherbrooke, Que., Canada.
Kachadourian
Rémy
R
Lemay
Rosalie
R
Bisson
Martine
M
Day
Brian J
BJ
Paquette
Benoit
B
D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004583:Electrons; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005609:Free Radicals; D020249:Hormone Replacement Therapy; D007477:Ions; D019787:Linoleic Acid / Q000494:pharmacology; D015227:Lipid Peroxidation; D013058:Mass Spectrometry; D008956:Models, Chemical; D016877:Oxidants / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption
D000975:Antioxidants; D004967:Estrogens; D005609:Free Radicals; D007477:Ions; D016877:Oxidants; D004970:Estrone; D004958:Estradiol; D003300:Copper; D004247:DNA; D019787:Linoleic Acid; D010100:Oxygen