Study on the Biomolecular Competitive Mechanism of Polybrominated Diphenyl Ethers and Their Derivatives on Thyroid Hormones

Shaoheng Liu; Rong Hu; Hao Zhan; Wanli You; Jianjun Tao; Luhua Jiang

doi:10.3390/molecules28217374

Study on the Biomolecular Competitive Mechanism of Polybrominated Diphenyl Ethers and Their Derivatives on Thyroid Hormones

Molecules. 2023 Oct 31;28(21):7374. doi: 10.3390/molecules28217374.

Authors

Shaoheng Liu¹, Rong Hu², Hao Zhan³, Wanli You¹, Jianjun Tao¹, Luhua Jiang⁴

Affiliations

¹ Engineering Research Center of Hunan Province for Recycling Technology of Electroplating Wastewater, Hunan Provincial Key Laboratory of Water Treatment Functional Materials, College of Chemistry and Material Engineering, Hunan University of Arts and Science, Changde 415000, China.
² College of Environment, South China Normal University, Guangzhou 510006, China.
³ College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541006, China.
⁴ Key Laboratory of Biometallurgy of Ministry of Education, College of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China.

Abstract

Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants. PBDEs and their derivatives, hydroxylated PBDEs (OH-PBDEs), can bind to hormone receptors and impact hormone secretion, transportation, and metabolism, leading to endocrine disruption and the development of various diseases. They have particularly strong interference effects on thyroid hormones. This study used decabromodiphenyl ether (BDE-209); 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); and 6-OH-BDE-47 as representative compounds of PBDEs and their derivatives, OH-PBDEs. A fluorescence probe, fluorescein-isothiocyanate-L-thyroxine (FITC-T4, F-T4), specific for binding to transthyretin (TTR), a thyroid transport protein, was prepared. The binding capacity of PBDEs and their derivatives, OH-PBDEs, to TTR was quantitatively measured using fluorescence spectroscopy. The principle of quenching the fluorescence intensity of F-T4 after binding to TTR was used to analyze the competitive interaction between the probe and BDE-209, BDE-47, and 6-OH-BDE-47, thereby evaluating the toxic effects of PBDEs and their derivatives on the thyroid system. Additionally, AutoDock molecular docking software (1.5.6) was used to further analyze the interference mechanism of OH-PBDEs on T4. The results of the study are as follows: (1) Different types of PBDEs and OH-PBDEs exhibit varying degrees of interference with T4. Both the degree of bromination and hydroxylation affect their ability to competitively bind to TTR. Higher bromination and hydroxylation degrees result in stronger competitive substitution. (2) The competitive substitution ability of the same disruptor varies at different concentrations. Higher concentrations lead to stronger substitution ability, but there is a threshold beyond which the substitution ability no longer increases. (3) When OH-PBDEs have four or more bromine atoms and exhibit the most structural similarity to T4, their binding affinity to TTR is stronger than that of T4.

Keywords: OH-PBDEs; PBDEs; fluorescence probe; molecular docking; thyroid interference.

MeSH terms

Halogenated Diphenyl Ethers* / chemistry
Hydroxylation
Molecular Docking Simulation
Thyroid Hormones*

Substances

decabromobiphenyl ether
2,2',4,4'-tetrabromodiphenyl ether
Halogenated Diphenyl Ethers
6-OH-BDE-47
Thyroid Hormones

Abstract

MeSH terms

Substances

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