1994 Volume 41 Issue 6 Pages 605-611
In order to clarify the mechanism of antiatherogenic action of several steroids such as estrogens, dehydroepiandrosterone (DHEA) and dexamethasone, we investigated the effects of various steroids on the copper (Cu2+)-catalyzed oxidation of low density lipoprotein (LDL) or high density lipoprotein (HDL) in 0.15 M NaCl by measuring thiobarbituric acid-reactive substances (TBARS). At a concentration of 10-5 M, estrogens strongly protected against LDL oxidation by 0.5 μM Cu2+ in the following order of inhibition: estradiol (E2)(75%), estrone (E1)(35%) and estriol (E3)(30%). However, the corresponding metabolites of these estrogens, the catechol estrogens, had an even more protective effect on LDL oxidation by 0.5 iM Cu2+ in the following order of inhibition: 2-hydroxyestradiol (2-OHE2)(98%), 2-OHE1 (97%) and 2-OHE3 (96%). E2 and 2-OHE2 from 10-7 M to 10-5 M inhibited LDL oxidation in a dose-dependent manner, with a more marked effect for oxidation by 0.1μM Cu2+ than by 0.5μM Cu2+. 10-5 M dexamethasone produced a slight (10%) but significant inhibition of LDL oxidation by 0.5 μM Cu2+. In addition, the estrogens and catechol estrogens were also effective in protecting against HDL oxidation by 0.5μM Cu2+. Other steroids including DHEA and DHEA-sulfate had no antioxidative effects on either LDL or HDL in this system. These results indicate that estrogens and their metabolites, the catechol estrogens, exert antioxidative effects on both LDL and HDL. The catechol estrogens may be more important antioxidants than estrogens for both LDL and HDL. Dexamethasone may exert its antiatherogenic effect partly by inhibiting the oxidation of lipoproteins, but this may not be the case for DHEA and DHEA-sulfate.
