Concentration Dependence of Prooxidant and Antioxidant Properties of Catecholestrogens

Markides, Constantine; Roy, Deodutta; Liehr, Joachim G.

doi:10.1006/abbi.1998.0934

Cited by 64 publications

(27 citation statements)

References 41 publications

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“…In contrast to their effects on native LDL, our ultrafiltrates of below 500 Da possessed prooxidant activity toward mildly oxidized LDL. Similar observations have been reported for a number of different purified compounds (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), but this is the first report that a human biological fluid, similar in some ways to that which may be present within the arterial wall, can either promote or inhibit LDL oxidation depending upon the oxidation state of the lipoprotein.…”

Section: Discussionsupporting

confidence: 86%

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Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid

Patterson

Horsley

Leake

2003

Journal of Lipid Research

132

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Section: Discussionsupporting

confidence: 86%

“…Antioxidant to prooxidant switches have since been reported for a number of different compounds, including dehydroascorbate (12), flavonoids (13), caffeic and chlorogenic acid (14), catecholestrogens (15), ferulic acid (16), Trolox C (a water-soluble analog of vitamin E) (17), aminoguanidine (18), and uric acid (19,20).…”

mentioning

confidence: 99%

Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid

Patterson

Horsley

Leake

2003

Journal of Lipid Research

132

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“…In this context, 2-ME inhibited neointima formation by inhibiting smoothmuscle cell growth [14], and exerted cardiovascularprotective effects in a model of severe cardiovascular and renal injury [15,16]. In addition, 2-ME reduced oxidative stress [14,22] in smooth muscle cells, and increased prostacyclin in endothelial cells [23]. Our study showed for the first time that 2-ME reduces monocyte adhesion to endothelial cells in vivo without affecting body weight, serum parameters, and blood pressure.…”

Section: Discussionmentioning

confidence: 70%

2-Methoxyestradiol Reduces Monocyte Adhesion to Aortic Endothelial Cells in Ovariectomized Rats

et al. 2007

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Abstract. 2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with no affinity for estrogen receptors. It inhibits cell proliferation, thus is a potentially useful drug to block the progression of atherosclerosis. As a first step to examining the anti-atherosclerotic effects of 2-ME, we investigated monocyte adhesion to aortic endothelial cells, which is considered a prerequisite to atherosclerosis in vivo. Eight-week-old Sprague-Dawley rats were ovariectomized then treated by slow-release pellets with placebo, 17-β-estradiol (5 µg/day), low-dose 2-ME (10 µg/day), or high-dose 2-ME (100 µg/day). After 6 weeks, enface analysis showed an increased number of monocytes adhering to endothelial cells of the thoracic aorta in ovariectomized rats compared with sham-operated controls. This increase was predominantly inhibited by treatment with 17β-estradiol, and low-dose or high-dose 2-ME. The observed effects were unrelated to changes in serum lipids, blood glucose, or blood pressure. Our data suggested that 2-ME mediates the anti-atherosclerotic actions of estradiol at least in part by preventing monocyte adhesion to the aortic endothelium. CARDIOVASCULAR disease is a major cause of morbidity and mortality in modern societies. In women, menopause increases the risk of cardiovascular disease [1, 2], probably due to reduced estrogen levels [3][4][5]. Hormone replacement therapy is reported to delay the onset of cardiovascular disease in postmenopausal women [6,7]. In contrast, two major randomized prospective clinical trials, the Heart and Estrogen/progestin Replacement Study (HERS) [8] and the Women's Health Initiative Study (WHI) [9], found that hormone replacement therapy increased the risk of cardiovascular disease following menopause. This discrepancy might reflect differences in study conditions. The efficacy of hormone replacement therapy to protect against atherosclerosis seems dependent on the atherosclerotic state, type of estrogen used, and the coadministration of progestin [10]. Research into the anti-atherosclerotic effect of estrogen is thus needed to establish a better method to deliver estrogen to postmenopausal women. The endogenous estrogen 17β-estradiol (E 2 ) binds to both estrogen receptor (ER) α and β. Activation of ERα and β has been linked with some, but not all, antiatherosclerotic effects of estrogen [11][12][13]. 2-methoxyestradiol (2ME), a metabolite of estradiol with no affinity for estrogen receptors, is a potent inhibitor of cell proliferation, tumor growth, and angiogenesis, and might, at least in part, mediate anti-atherosclerotic effects of estrogen [14][15][16][17]. Abbreviations: E 2 : 17β-estradiol, ER: estrogen receptor, FFA: free fatty acid, 2-ME: 2-methoxyestradiol, NEMOes: New enface method for optimal observation of endothelial surface, TC: total cholesterol, TG: triglyceride.

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“…and oxidation of low-density lipoproteins in vitro (8,14), and increases cyclooxygenase-2 expression and prostacyclin generation (11,23), all participants in atherogenesis (10,24,25).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, 2-methoxyestradiol has vasculoprotective effects in rat models of drug-induced hypertension and pulmonary hypertension (12,13) and reduces the oxidation of low-density lipoprotein in vitro (14), raising the question of whether 2-methoxyestradiol might have antiatherosclerotic effects. Hypotheses that 2-methoxyestradiol can modulate atherogenesis (10) currently remain untested in vivo.…”

mentioning

confidence: 99%

The Endogenous Estradiol Metabolite 2-Methoxyestradiol Reduces Atherosclerotic Lesion Formation in Female Apolipoprotein E-Deficient Mice

et al. 2007

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Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell proliferation independently of the classical estrogen receptors. This study examined whether 2-methoxyestradiol affects atherosclerosis development in female mice. Apolipoprotein E-deficient mice, a well-established mouse model of atherosclerosis, were ovariectomized and treated through slowrelease pellets with placebo, 17␤-estradiol (6 g/d), or 2-methoxyestradiol [6.66 g/d (low-dose) or 66.6 g/d (high-dose)]. After 90 d, body weight gain decreased and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol group. En face analysis showed that the fractional area of the aorta covered by atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels decreased in the high-and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and 21%, P ‫؍‬ 0.062, respectively). Estradiol treatment reduced the fractional atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In conclusion, our study shows for the first time that 2-methoxyestradiol reduces atherosclerotic lesion formation in vivo.

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Concentration Dependence of Prooxidant and Antioxidant Properties of Catecholestrogens

Cited by 64 publications

References 41 publications

Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid

Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid

2-Methoxyestradiol Reduces Monocyte Adhesion to Aortic Endothelial Cells in Ovariectomized Rats

The Endogenous Estradiol Metabolite 2-Methoxyestradiol Reduces Atherosclerotic Lesion Formation in Female Apolipoprotein E-Deficient Mice

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