The effect of 17β-estradiol and α-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of γ-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 (E-2), the liposoluble vitamin E (both, alpha- and gamma-tocopherol), and melatonin. Design: 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 mu M of CuSO4 to induce oxidative stress and with one of the four compounds studied: E-2, alpha-tocopherol, gamma-tocopherol, or melatonin in doses of 0, 5, 15, 50, and 500 mu M and 1 and 2 mM. Malondialdehyde (MDA) was measured as a marker of LDL oxidation, Results: E-2 induced a dose-dependent decrease in MDA concentration (nmol/mg protein). MDA values were significantly different as compared with baseline at 5 mu M of E-2 (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 mu M with alpha-tocopherol, 500 mu M with melatonin, and 1 mM with gamma-tocopherol. The antioxidant effect also reached a plateau at concentrations of 50 mu M of E-2 and 1 mM of alpha-tocopherol; gamma-tocopherol and melatonin did not reach a plateau at any dose tested. Conclusions: The antioxidant potency of E-2 in vitro is at least 10-100 times greater than alpha- and gamma-tocopherol and melatonin. Whether this finding implies a better performance of E-2 as a protective agent against oxidation-related diseases remains to be determined. (Menopause 2000;7:112-116. (C) 2000, The North American Menopause Society.).