Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0·25 and 0·5%). In the rats fed 0·5%, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7·0% in OVX rats treated with Hp (HpOVX) and +6·6% in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P<0·05). In the rats fed 0·25% hesperetin equivalents, the H-7-glcOVX group showed a 6·6% improvement in total femoral BMD v. the OVX controls (P<0·05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0·25% H-7-glc was equal to that of those given 0·5% Hp, but was not further increased at 0·5% H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compoun

Développement d'un outil bio-moléculaire pour la détection des composés à action oestrogénique présents dans l'environnement

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Review Article Assessment and Molecular Actions of Endocrine-Disrupting Chemicals That Interfere with Estrogen Receptor Pathways

Copyright © 2013 Gwenneg Kerdivel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In all vertebrate species, estrogens play a crucial role in the development, growth, and function of reproductive and nonreproductive tissues. A large number of natural or synthetic chemicals present in the environment and diet can interfere with estrogen signaling; these chemicals are called endocrine disrupting chemicals (EDCs) or xenoestrogens. Some of these compounds have been shown to induce adverse effects on human and animal health, and some compounds are suspected to contribute to diverse disease development. Because xenoestrogens have varying sources and structures and could act in additive or synergistic effects when combined, they have multiple mechanisms of action. Consequently, an important panel of in vivo and in vitro bioassays and chemical analytical tools was used to screen, evaluate, and characterize the potential impacts of these compounds on humans and animals. In this paper, we discuss different molecular actions of some of the major xenoestrogens found in food or the environment, and we summarize the current models used to evaluate environmental estrogens. 1

Effects of estrogens and endocrine-disrupting chemicals on cell differentiation-survival-proliferation in brain: contributions of neuronal cell lines.

International audienceEstrogens and estrogen receptors (ER) are key actors in the control of differentiation and survival and act on extrareproductive tissues such as brain. Thus, estrogens may display neuritogenic effects during development and neuroprotective effects in the pathophysiological context of brain ischemia and neurodegenerative pathologies like Alzheimer's disease or Parkinson's disease. Some of these effects require classical transcriptional "genomic" mechanisms through ER, whereas other effects appear to rely clearly on "membrane-initiated mechanisms" through cytoplasmic signal transduction pathways. Disturbances of these mechanisms by endocrine-disrupting chemicals (EDC) may exert adverse effects on brain. Some EDC may act via ER-independent mechanisms but might cross-react with endogenous estrogen. Other EDC may act through ER-dependent mechanisms and display agonistic/antagonistic estrogenic properties. Because of these potential effects of EDC, it is necessary to establish sensitive cell-based assays to determine EDC effects on brain. In the present review, some effects of estrogens and EDC are described with focus on ER-mediated effects in neuronal cells. Particular attention is given to PC12 cells, an interesting model to study the mechanisms underlying ER-mediated differentiating and neuroprotective effects of estrogens

Estrogen receptor preparation effects on the receptor–DNA interaction by surface plasmon resonance

International audienceUp to now, several studies have investigated estrogen receptor (ER)–estrogen response element (ERE) interaction using biosensors such as surface plasmon resonance. These strategies have aimed to understand the molecular mechanism of such interaction as well as the effect of the ligand on this interaction. These approaches start to be used to determine the mechanisms of protein/DNA interaction, in particular in the context of drug discovery or environmental applications. However, some physical and biochemical parameters (incubation time, temperature, protease inhibitor cocktail, and bovine serum albumin (BSA)) are not completely described in the literature and could deeply modify the obtained results. This paper aims to focus not only on the preliminary steps of sample preparation such as protein thawing and incubation conditions (time and temperature) but also on the evaluation of protease inhibitor cocktail and BSA effect on the measurement of ER–ERE interactions

Determination of estrogen presence in water by SPR using estrogen receptor dimerization

International audienceEstrogenic compounds are a class of pharmaceutical products harmful to animals and a cause of environmental damage. The biological activity of these compounds is high since they have been designed to act at low concentrations. Thus, even at the low concentrations found in the environment, they may produce deleterious effects on aquatic organisms as well as on humans, who might be contaminated in a number of ways (via drinking water or contaminated food, for example). We used the property of these compounds to bind a specific protein (estrogen receptor, ER) to develop a quantification method of these chemical entities. Estrogenic compound detection was performed using ER dimerization properties monitored by surface plasmon resonance (SPR). The ligand-activated ER dimer was detected by its interaction with a specific DNA consensus sequence estrogen response element. The concentration and the nature of the estrogenic compounds modified the SPR signal and were characteristic of the ligand-dependent homodimerization of ER. For 17β-estradiol, dimerization of ER was experimentally determined at an ER to 17β-estradiol ratio near 1:1. Estrogenic compounds (17β-estradiol, estriol, estrone, ethynyl estradiol) activated the dimerization process at different concentration levels, while some others (tamoxiphen, resveratrol, genistein, bisphenol A) did not seem to have any effects on it. We demonstrated that this method allows the direct detection of 17β-estradiol at concentrations above 1.4 μg/L (5 nM)

Rapid assessment of estrogenic compounds by CXCL-test illustrated by the screening of the UV-filter derivative benzophenones.

International audienceCXCL-test is a method that uses the estrogen-dependent secretion of the natural endogenous chemokine CXCL12 to evaluate the estrogenic activity of molecules. CXCL12 chemokine is involved in the estrogen dependent proliferation of breast cancer cells. Its measure is an indicator of cell proliferation and is used as an alternative test to classical proliferation test. Here we aimed to optimize this test, first to increase the number of tested molecules in a single assay and then to decrease the number of intermediate steps. The optimized CXCL-test was finally used for the evaluation of the estrogenic potency of emerging chemical pollutants: the UV filter benzophenones (BPs). The effect of BPs on CXCL12 secretion was also validated by real time quantitative RT-PCR. The optimized CXCL-test allowed a fast and direct assessment of estrogenic potency of molecules. The estrogenic activities of benzophenones were characterized and divided in two groups. The first one contains weak estrogenic compounds (BP, BP1, BP2, BP3, 234BP and 2344′BP). The second one contains medium estrogenic compounds (4BP, 44′BP, BP8, THB)

Emerging Estrogenic Pollutants in the Aquatic Environment and Breast Cancer

International audienceThe number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways. They represent a potential risk for human and wildlife as they are suspected to be involved in the development of diseases including, but not limited to, reprotoxicity, metabolic disorders, and cancers. More precisely, several studies have suggested that the increase of breast cancers in industrialized countries is linked to exposure to EDCs, particularly estrogen-like compounds. Estrogen receptors alpha (ERα) and beta (ERβ) are the two main transducers of estrogen action and therefore important targets for these estrogen-like endocrine disrupters. More than 70% of human breast cancers are ERα-positive and estrogen-dependent, and their development and growth are not only influenced by endogenous estrogens but also likely by environmental estrogen-like endocrine disrupters. It is, therefore, of major importance to characterize the potential estrogenic activity from contaminated surface water and identify the molecules responsible for the hormonal effects. This information will help us understand how environmental contaminants can potentially impact the development of breast cancer and allow us to fix a maximal limit to the concentration of estrogen-like compounds that should be found in the environment. The aim of this review is to provide an overview of emerging estrogen-like compounds in the environment, sum up studies demonstrating their direct or indirect interactions with ERs, and link their presence to the development of breast cancer. Finally, we emphasize the use of in vitro and in vivo methods based on the zebrafish model to identify and characterize environmental estrogens