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In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish
Örebro University, School of Science and Technology.ORCID iD: 0000-0003-3302-7106
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.
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(English)Manuscript (preprint) (Other academic)
Keyword [en]
Brominated flame retardants, stereoidgenesis, gene regulation, hatch, teratogenesis
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:oru:diva-43911OAI: oai:DiVA.org:oru-43911DiVA: diva2:798896
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Interaction of brominated flame retardants with the chicken and zebrafish androgen receptors
Open this publication in new window or tab >>Interaction of brominated flame retardants with the chicken and zebrafish androgen receptors
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The survival of organisms depends on their ability to use different signaling pathways to adapt to the environment. The endocrine system consists of glands that release hormones to the blood stream. Male reproductive functions are regulated by androgens through interactions with the androgen receptor (AR). AR has been characterized in chicken and zebrafish where they use testosterone and 11-ketotestosterone as their primary androgens, respectively. AR function has been disturbed by different endocrine disrupting compounds (EDCs) present in the environment causing detrimental effects on avian and fish species. Brominated flame retardants (BFRs) are a group of EDCs that are ubiquitous in the environment. Molecular modeling techniques using computer simulations such as docking and molecular dynamics are a useful tool in the identification of EDCs. The capacity to test thousands of compounds at once has helped in the early identification of EDCs that interact with AR. Two groups of BFRs, the 1,2-dibromo-4- cyclohexane diastereomers (TBECH) and the compounds synthesized from 2, 4, 6-tribromophenol, allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6- tribromophenyl ether (BATE) and 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE) interact and alter AR activity in human in vitro studies. As models for avian and fish species, chicken and zebrafish were used to test these BFRs. TBECH diastereomers were able to bind to the AR, estrogen receptors and thyroid receptors in the chicken and to the AR in zebrafish. ATE, BATE and DPTE were also able to interact with the chicken AR and zebrafish AR. Activation studies using cell lines showed that TBECH diastereomers acted as agonists to the cAR and zAR while ATE, BATE and DPTE acted as antagonists. The BFRs also altered multiple signaling pathways such as the apoptotic, antiapoptotic, immune, drug metabolizing and DNA methylation systems and in vivo studies resulted in physiological effects on zebrafish.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2015. 70 p.
Series
Örebro Studies in Life Science, 12
Keyword
DBE-DBCH, TBP-AE, TBP-BAE, TBP-DBPE, gene transcription
National Category
Biological Sciences
Research subject
Biology
Identifiers
urn:nbn:se:oru:diva-42881 (URN)978-91-7529-067-6 (ISBN)
Public defence
2015-04-29, Hörsalen, Musikhögskolan, Örebro universitet, Fakultetsgatan 1, Örebro, 10:00 (English)
Opponent
Supervisors
Available from: 2015-02-23 Created: 2015-02-23 Last updated: 2017-10-17Bibliographically approved

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