The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin.
OBJECTIVE
Estrogens have a potent antioxidant effect on low-density lipoprotein (LDL) cholesterol in vitro and in vivo. A variety of compounds with antioxidant properties, such as vitamins and other hormones, also have been recommended in clinical practice to prevent several diseases related to oxidation. The aim of this study was to compare the antioxidant potency of estradiol (E2), the liposoluble vitamin E (both, alpha- and gamma-tocopherol), and melatonin.


METHODS
LDL was isolated by ultracentrifugation from the plasma of 11 healthy, untreated postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with 15 microM of CuSO4 to induce oxidative stress and with one of the four compounds studied: E2, alpha-tocopherol, gamma-tocopherol, or melatonin in doses of 0, 5, 15, 50, and 500 microM and 1 and 2 mM. Malondialdehyde (MDA) was measured as a marker of LDL oxidation.


RESULTS
E2 induced a dose-dependent decrease in MDA concentration (nmol/mg protein). MDA values were significantly different as compared with baseline at 5 microM of E2 (F = 47.17; p < 0.0001). Alpha-tocopherol, gamma-tocopherol, and melatonin also showed a significant decrease in MDA concentration but to a lesser degree. The reduction of MDA reached statistical significance at 50 microM with alpha-tocopherol, 500 microM with melatonin, and 1 mM with gamma-tocopherol. The antioxidant effect also reached a plateau at concentrations of 50 microM of E2 and 1 mM of alpha-tocopherol; gamma-tocopherol and melatonin did not reach a plateau at any dose tested.


CONCLUSIONS
The antioxidant potency of E2 in vitro is at least 10-100 times greater than alpha- and gamma-tocopherol and melatonin. Whether this finding implies a better performance of E2 as a protective agent against oxidation-related diseases remains to be determined.
Arteaga
E
E
Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago.
Rojas
A
A
Villaseca
P
P
Bianchi
M
M
D000975:Antioxidants / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology; D008875:Middle Aged; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D008078:Cholesterol, LDL; D014810:Vitamin E; D004958:Estradiol; D008550:Melatonin