<i>In Vitro</i> and <i>in Silico</i> Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins

Hill, Katie; Mortensen, Åse-Karen; Teclechiel, Daniel; Willmore, William G.; Sylte, Ingebrigt; Jenssen, Bjørn Munro; Letcher, Robert J.

doi:10.1021/acs.est.7b04617

Cited by 21 publications

(9 citation statements)

References 37 publications

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“…Typically, the toxicity of a BFR is evaluated without considering degradation products, even though it was shown that the degradation of a BFR can alter its toxic potential. − Especially for polymeric BFRs, which are claimed to be more environmental friendly, degradation products should be considered. In a previous study dealing with “Polymeric FR”, possible structures of such products were listed.…”

Section: Discussionmentioning

confidence: 99%

Degradation of the Polymeric Brominated Flame Retardant “Polymeric FR” by Heat and UV Exposure

Koch

Nachev

Klein

et al. 2019

Environ. Sci. Technol.

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Monomeric brominated flame retardants often pose risks to the environment. The new group of polymeric flame retardants is claimed to be a safer alternative due to their high molecular weight and persistence by design. Within this publication, the degradation of a commercially widely applied example of this groupthe polymer "Polymeric FR"was studied during UV irradiation and long-term exposure to heat (60 °C) for up to 36 weeks. Both treatments led to a variety of degradation products, which might have potentially adverse environmental effects and an increased mobility compared to the mother polymer. Besides identifying some of the possible degradation products (including for instance 2,4,6tribromo-3-hydroxybenzoic acid), the degradation via UV irradiation, which yields 75 different degradation products, and via heat, which led to significantly less products, was compared. In addition, further parameters like TOC and the concentration of free bromine were studied and it was demonstrated that the used type of water (distilled, reconstituted, and rainwater) does not influence the outcome of the degradation experiments.

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Section: Discussionmentioning

confidence: 99%

Degradation of the Polymeric Brominated Flame Retardant “Polymeric FR” by Heat and UV Exposure

Koch

Nachev

Klein

et al. 2019

Environ. Sci. Technol.

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“…The halogen elements are like to iodine structurally, competing for uptake and utilization, and can replace each other in physiological reactions. Competition between iodine and the other halogens in binding to T4 at position 5 is a potential thyroid disruptor mechanism, and this happens when iodine is in lesser amounts than uorine, bromine or iodine (13). The synthesis of T4 takes place exclusively in the thyroid, and the iodine in the T4 molecule can be substituted in its aromatic rings, which in turn are linked by a diphenylether moiety, adopting different con gurations that allow different intra-and intermolecular interactions (14).…”

Section: Discussionmentioning

confidence: 99%

Halogens as Potential Thyroid Disruptors – In Sílico Simulation and Mathematical Model for Triggering Autoimmune Thyroiditis

Andrade

Oliveira

Bittencourt

et al. 2023

Preprint

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Introduction The halogens are the non-metallic chemical elements belonging to group 17 of the Periodic Table, namely: fluorine, chlorine, bromine, iodine, astate, and teness. Halogens are biologically atypical components, however are frequent as replacement in the binders of the thyroid hormones and inhibitors, binding precisely to nucleic acids and proteins. Objective Simulate in sílico and through a mathematical model the interactions between the ionic changes in the thyroxine (T4) molecule in the process of autoimmunity induction. Methods We used an online application to simulate the docking of fluorine, chlorine, and bromine in the T4 molecule in place of iodine. A hypothetical-deductive mathematical model was assembled to evaluate halogen substitution in the T4 molecule and immune system and its correlation with the development of autoimmune thyroiditis. Results Simulation of the coupling of fluorine, chlorine and bromine, instead of iodine, to T4 were successful using the induced fit docking program. Positioning of each halogen ion in replacing the iodine at position 5 of T4 was achieved. The mathematical model used demonstrated that the change of the halogen ion in the T4 molecule has been shown to be the trigger for the autoimmune trigger of thyroiditis. Conclusion The findings from this study suggest that halogens of lower atomic weight than iodine may act as a trigger for the onset of autoimmune thyroiditis.

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“…Whether these transcriptional effects are compensatory mechanisms in response to a reduction in thyroid synthesis and transport to target tissues or whether in ovo exposure to BTBPE, EHTBB, and TBPH causes over stimulation of the thyroid system is unclear. There is some evidence that BTBPE and EHTBB inhibit deiodinase enzyme activity [ 30 ], and studies in glaucus ( Larus hyperboreus ) and herring gulls ( L. argentatus ) suggest that flame retardants may competitively bind to transthyretin [ 31 , 32 ]. Therefore, it is possible that upregulation of DIO genes and TTR in male kestrel hatchlings may be a compensatory response to counteract inhibition of deiodinase activity and lower levels of transthyretin.…”

Section: Discussionmentioning

confidence: 99%

Hepatic Gene Expression Profiling of American Kestrels (Falco sparverius) Exposed In Ovo to Three Alternative Brominated Flame Retardants

Goodchild

Karouna‐Renier

Braham

et al. 2022

Biology

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A number of brominated flame retardants (BFRs) have been reported to interfere with the thyroid signaling pathway and cause oxidative stress in birds, yet the underlying shifts in gene expression associated with these effects remain poorly understood. In this study, we measured hepatic transcriptional responses of 31 genes in American kestrel (Falco sparverius) hatchlings following in ovo exposure to one of three high-volume alternative BFRs: 1,2-bis(2,4,6-tribromophenoxy) ethane (BTPBE), bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), or 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB). Hatchling kestrels exhibited shifts in the expression of genes related to oxidative stress (CYP, GSTA, SOD, and GPX1), thyroid hormone metabolism and transport (DIO1, DIO2, and TTR), lipid and protein metabolism (PPAR, HMGCR, FAB1, and LPL), and cytokine-mediated inflammation (TLR3, IL18, IRF7, STAT3, RACK1, and CEBPB). Male and female hatchlings differed in which genes were differentially expressed, as well as the direction of the effect (up- vs. downregulation). These results build upon our previous findings of increased oxidative stress and disrupted thyroid signaling pathway in the same hatchlings. Furthermore, our results indicate that inflammatory responses appear to occur in female hatchlings exposed to BTBPE and EHTBB in ovo. Gene expression analysis revealed multiple affected pathways, adding to the growing evidence that sublethal physiological effects are complex and are a concern for birds exposed to BTBPE, EHTBB, or TBPH in ovo.

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In Vitro and in Silico Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins

Cited by 21 publications

References 37 publications

Degradation of the Polymeric Brominated Flame Retardant “Polymeric FR” by Heat and UV Exposure

Degradation of the Polymeric Brominated Flame Retardant “Polymeric FR” by Heat and UV Exposure

Halogens as Potential Thyroid Disruptors – In Sílico Simulation and Mathematical Model for Triggering Autoimmune Thyroiditis

Hepatic Gene Expression Profiling of American Kestrels (Falco sparverius) Exposed In Ovo to Three Alternative Brominated Flame Retardants

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