Evidence for the role of high density lipoproteins in mediating the antioxidant effect of estrogens

Abstract

Estrogens possess strong antioxidant effects in vitro, but in vivo studies in humans have yielded conflicting results. Little is known regarding factors that mediate the antioxidant effect of estrogens in vivo. In this study the potential role of high density lipoprotein (HDL) was examined. The antioxidant effect of estradiol-17b (E2) added to low density lipoprotein (LDL) was lost after dialysis. In contrast, the antioxidant effect of E2 added to HDL was conserved after dialysis, suggesting that E2 was bound to HDL. Binding of E2 to LDL increased after esterification (especially to long chain fatty acids). In the presence of HDL, an increased amount of E2 was transferred to LDL. E2-17 ester was as potent as E2 in preventing LDL oxidation in vitro, but 3,17-diesters were not as effective (E2 = E2-17 ester > E2-3 ester > E2-3,17 diester). This was also supported by experiments which showed that estrogens with masked 3-OH groups were not effective as antioxidants. These studies provide evidence that HDL could facilitate the antioxidant effect of E2 through initial association, esterification and eventual transfer of E2 esters to LDL. Therefore it is critical that HDL peroxidation parameters be evaluated in subjects receiving estrogen replacement therapy.

Assignment of the Binding Site for Haptoglobin on Apolipoprotein A-I

“…Actually, Hpt was found to inhibit ApoA-I-dependent LCAT activity in vitro (23) and to associate with low reverse cholesterol transport in human ovarian follicular fluid (24). In addition, estradiol esterification in the follicle and ester delivery through HDL-mediated circulation to storage tissue (25,26) for long acting hormonal and antioxidant function (27,28) might be influenced by defective reverse cholesterol transport and reduced LCAT activity (24).…”

Role of plasma lipoproteins in the transport of the soyabean isoflavones daidzein and daidzein-7-O-β-d-glucoside

“…The concentrations of DAI in the different fractions obtained after lipoprotein separation of 2 ml plasma were measured by GC/MS using a stable isotopically labelled internal standard [3,4,[8][9][10][11][12][13] C]DAI. Total DAI was determined after extraction and enzymic hydrolysis with a mix of b-glucuronidase and sulfatase.…”

“…The separated lipoprotein fractions were equilibrated with 100 pmol [3,4,[8][9][10][11][12][13] C]DAI for 30 min at room temperature and diluted with five volumes of 0·5 M-triethylammonium sulfate (pH 5). Further details on sample clean-up, enzymic hydrolysis and derivatisation for GC/MS analysis are described by Rüfer et al (4) .…”

“…GC/MS conditions can be found in Rüfer et al (4) . The selected ion monitoring was applied to monitor two ions for each analyte, where the first was used for quantification and the second was used as confirmation of the presence of the analyte: m/z 398 and 383 for DAI as well as m/z 401 and 386 for [3,4,[8][9][10][11][12][13] C]DAI. DAI was quantified using ten calibration levels between 0 and 10 pmol.…”

“…[3,4,[8][9][10][11][12][13] C]DAI was obtained from Nigel Botting, University of St Andrews (St Andrews, UK). Enzymes and all other chemicals used were obtained from SigmaAldrich (Taufkirchen, Germany).…”