Abstract
Oxidized low density lipoproteins (LDL) are believed to play a central role in the
events that initiate atherosclerosis. Antioxidants have been shown to decrease the
oxidation of LDL, leading to the diminution of atherosclerosis. Since it is well-known
that decreased levels of dehydroepiandrosterone (DHEA) are linked to the development
of atherosclerosis, we studied the modulation of the oxidation of LDL by DHEA. LDL
were obtained from 10 healthy subjects and oxidized by free radicals produced by γ-radiolysis of ethanol–water mixtures. The formation of conjugated dienes and thiobarbituric
acid-reactive substances (TBARS), the vitamin E content, as well as the incorporation
of 4-[14C]DHEA in LDL and the chemotactic effect of oxidized LDL in the presence of DHEA towards
monocytes, were investigated. It was found that DHEA was able to inhibit the oxidation
of LDL by reducing over 90% of the conjugated dienes and TBARS formation, as well
as by reducing the vitamin E disappearance and significantly decreasing the chemotactic
activity towards monocytes. Our results suggest that DHEA exerts its antioxidative
effect by protecting the endogenous vitamin E of LDL.
Keywords
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References
- Cell biology of atherosclerosis.Annu Rev Physiol. 1995; 57: 791-804
- Anti-atherogenic effect of probucol is unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low-density lipoprotein degradation in macrophage rich fatty streaks and slow progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit.Proc Natl Acad Sci USA. 1987; 84: 7725-7729
- Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation?.J Clin Invest. 1994; 94: 155-164
- The role of lipid peroxidation and antioxidants in oxidative modification of LDL.Free Rad Biol Med. 1992; 13: 341-390
- Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant.Biochem J. 1992; 288: 341-344
- Estrogens as natural antioxidants of membrane phospholipid peroxidation.FEBS Lett. 1987; 210: 37-39
- Inhibitory effect of female hormones on lipid peroxidation.Biochem Int. 1986; 13: 1051-1055
- The inhibition of low-density lipoprotein oxidation by 17-β estradiol.Metabolism. 1992; 41: 1110-1114
- Dehydroepiandrosterone (DHEA)—the multifunctional steroid. II. effects on CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of action?.Ann NY Acad Sci. 1994; 719: 564-575
- Activation of immune function by Dehydroepiandrosterone (DHEA) in age-advanced men.J Gerontol. 1997; 52A: M1-M7
- A radioimmunoassay for the estimation of serum dehydroepiandrosterone sulphate in normal and pathological sera.Clin Chim Acta. 1975; 65: 5-13
- Plasma dehydroepiandrosterone sulfate in normal and pathological conditions.J Clin Endocr. 1969; 29: 273-278
- Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults.J Clin Endocrinol Metab. 1980; 51: 330-333
- Dehydroepiandrosterone sulfate (DHEAS) in the oldest old aged 85 and over.Ann NY Acad Sci. 1994; 719: 543-552
- Relation between urinary androgen and corticoid excretion and subsequent breast cancer.Lancet. 1971; ii: 395-398
- A prospective study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease.New Engl J Med. 1986; 315: 1519-1524
- 17-ketosteroids and arteriosclerosis.Angiology. 1959; 10: 358-368
- Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography.J Am Coll Cardiol. 1990; 16: 862-870
- Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.J Clin Invest. 1988; 82: 2-720
- Dehydroepiandrosterone feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterolfed rabbit.Arteriosclerosis. 1989; 9: 159-166
- Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation.Circulation. 1993; 87: 261-269
- Hyperinsulinaemia and decreased plasma levels of dehydroepiandrosterone sulfate in premenopausal women with coronary heart disease.J Int Med. 1995; 237: 465-472
- Inhibition of growth of HeLa and W1-38 cells by dehydroepiandrosterone and its reversal by ribo- and desoxyribonucleosides.Life Sci. 1986; 38: 1451-1457
- Prevention of autoantibody formation and prolonged survival in New Zealand black/New Zealand white F1 mice fed dehydroepiandrosterone.J Clin Invest. 1985; 75: 2091-2093
- Protection against acute lethal viral infections with a native steroid dehydroepiandrosterone (DHEA).J Med Virol. 1988; 26: 301-314
- Dehydroepiandrosterone in vivo and in vitro inhibits palatelet aggregation.J Am Coll Cardiol. 1991; 17: 376A
- Rapid isolation of lipoproteins and assessment of their peroxidation by high performance liquide chromatography postcolumn chemiluminescence.Methods Enzymol. 1994; 233: 469-489
- The chemical action of Röntgen rays on dilute ferrosulfate solution as a measure of dose.Am J Roentgenol Radium Ther. 1927; 18: 430-432
- Effect of pH on the peroxidation of human high density lipoproteins (HDL) initiated by O2⋅−/HO2⋅ free radicals generated by water radiolysis.J Chim Phys. 1994; 91: 1132-1139
- A simple fluorometric assay for lipoperoxide in blood plasma.Biochem Med. 1976; 15: 212-216
- Physicochemical changes in human high density lipoproteins (HDL) oxidized by gamma-radiolysis generated oxyradicals.Biochim Biophys Acta. 1995; 1255: 23-30
- Determination of serum alpha tocopherol, (vitamin E) by high performance liquide chromatography.Clin Chem. 1978; 24: 585-590
- Lung alveolar epithelial cell migration in vitro: modulators end regulation processes.Am J Physiol. 1996; 270: L311-L319
- Effects of elastin peptides on human monocytes: Ca mobilization, stimulation of respiratory burst and enzyme secretion.Biochem Biophys Res Commun. 1987; 141: 92-98
Spinks JWT, Woods RJ. An Introduction to Radiation Chemistry, 3rd ed. Wiley, New York, 1990.
- Radiolysis of ethanol and ethanol–water solutions: a tool for studying bioradical reactions.Radiat Phys Chem. 1988; 32: 443-448
- Lipoprotein carriers of dehydropeiandrosterone fatty acid esters in human serum.J Steroid Biochem. 1989; 34: 559-561
- Curr Opin Lipidol. 1991; 2: 311-316
- Increased susceptibility of low-density lipoprotein (LDL) to oxidation by γ-radiolysis with age.FEBS Lett. 1996; 392: 45-48
- Androgenic and estrogenic metabolises in serum of mice fed dehydroepiandrosterone; relationship to antihyperglycemic effects.Metab Clin and Exp. 1987; 36: 863-869
- Estradiol protects against experimental cardiac transplant atherosclerosis.Transpl Proc. 1987; 19: 90-95
- Dehydroepiandrosterone and 16alpha-Br-epiandrosterone inhibit 12-O-tetradecanoylphorbol-13-acetate stimulation of superoxide radical production by human polymorphonuclear leukocytes.Carcinogenesis. 1985; 6: 333-335
- Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosteron-pretreated rats.Free Radic Res. 1994; 21: 427-435
- Antioxidant activity of dioscorea and dehyroepiandrosterone in older humans.Life Sci. 1996; 59: PL147-157
- Preservation of the endogenous antioxidants in low-density lipoproteins by ascorbate but not probucol during oxidative modification.J Clin Invest. 1991; 87: 597601
- Stopped-flow investigation of antioxidant activity of estrogens in solution.Biochim Biophys Acta. 1990; 1035: 348-352
- Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid binding globulin in human plasma.J Clin Endocrinol Metab. 1981; 53: 58-68
- Metabolic conversion of six steroid hormones by human high density lipoprotein.Biochim Biophys Acta. 1991; 1083: 18-28
- ZR-75-1 breast cancer cells generate nonconjugated steroids from low-density lipoprotein incorporated lipoidal dehydroepiandrosterone.Endocrinology. 1993; 133: 683-689
Article info
Publication history
Accepted:
August 4,
1997
Received in revised form:
July 28,
1997
Received:
March 26,
1997
Identification
Copyright
© 1998 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.