Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women.
OBJECTIVE
Oxidized low-density lipoprotein (LDL) seems to play an important role in the etiology of atherosclerosis. To further study this, we performed two studies: (1) we determined the ability of 10 estrogen components of the drug, conjugated equine estrogen (CEE), trans-resveratrol (t-resveratrol) and quercetin (red wine components), trolox (vitamin E analog), and probucol (a serum cholesterol-lowering drug) to delay or prevent the oxidation of plasma LDL isolated from untreated postmenopausal women, and (2) we assessed the effect of long-term (>1 year) estrogen replacement therapy and hormone replacement therapy on LDL oxidation by ex vivo methods.


METHODS
For the in vivo study, three groups of postmenopausal women were selected based on whether they were on long-term CEE therapy (group A: 0.625 mg CEE; n = 21), on combination CEE plus progestogen therapy (group B: 0.625 mg CEE + 5.0 mg medroxyprogesterone acetate, 10 days; n = 20), or not on any hormone therapy (group C; n = 37). For the in vitro study, only LDL samples obtained from group C were used. The kinetics of LDL oxidation were measured by continuously monitoring the formation of conjugated dienes followed by determination of the lag time.


RESULTS
All compounds tested protected the LDL from oxidative damage. The relative antioxidant potency of estrogen components was generally greater than that of the other compounds. The minimum dose (nmoles) required to double the lag time from the control lag time of 57 +/- 2 min was 0.47 for 17beta-dihydroequilenin, 17alpha-dihydroequilenin, Delta 8 -estrone; 0.6 to 0.7 for Delta 8 -17beta-estradiol, equilenin, and quercetin; 0.9 for 17beta-dihydroequilin and 17alpha-dihydroequilin; 1.3 for equilin, estrone, 17beta-estradiol, 17alpha-estradiol; 1.4 for trolox; 1.9 for probucol; and 3.0 for t-resveratrol. The data from the in vivo study indicate that after long-term estrogen replacement therapy (group A) and hormone replacement therapy (group B), the LDL was significantly ( p < 0.01) protected (higher lag time) against oxidation compared with the control (group C). There was no difference between groups A and B.


CONCLUSIONS
The oxidation of LDL isolated from postmenopausal women is inhibited differentially by various estrogens and other antioxidants. The unique ring B unsaturated estrogen components of CEE were the most potent, and t-resveratrol, the red wine component, was the least potent. Long-term CEE or CEE + medroxyprogesterone acetate administration to postmenopausal women protects the LDL against oxidation to the same extent. These combined data support the hypothesis that some of the cardioprotective benefits associated with CEE therapy and perhaps red wine consumption may be due to the ability of their components to protect LDL against oxidative modifications.
Bhavnani
B R
BR
Department of Obstetrics and Gynecology, Institute of Medical Sciences, University of Toronto, Ontario, Canada. bhavnani@smh.toronto.on.ca
Cecutti
A
A
Gerulath
A
A
Woolever
A C
AC
Berco
M
M
D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000517:prevention & control*; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000187:drug effects*; D008875:Middle Aged; D010084:Oxidation-Reduction; D017698:Postmenopause; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014920:Wine
D000975:Antioxidants; D002839:Chromans; D004966:Estrogens, Conjugated (USP); D008077:Lipoproteins, LDL; D013267:Stilbenes; D011794:Quercetin; D011341:Probucol; D000077185:Resveratrol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid