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RESEARCH ARTICLE

Structural studies on the endocrine-disrupting role of polybrominated diphenyl ethers (PBDEs) in thyroid diseases Ishfaq Ahmad Sheikh 1,2 & Mohd Amin Beg 1 Received: 5 March 2020 / Accepted: 26 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Polybrominated diphenyl ethers (PBDEs) are synthetic brominated flame retardants with extensive applications in daily-life consumer products. However, PBDEs have become ubiquitous environmental contaminants due to their leach-out capability. The hazardous human health effects and endocrine-disrupting activity of PBDEs have led many governmental organizations to impose ban on their manufacture, causing their gradual phase out from commercial products. However, PBDEs and their metabolites are still being detected from biological and environmental samples owing to their persistence and bioaccumulation. The PDBE metabolites in these samples are present in concentrations often higher and even with higher toxic potential than parent PBDEs. The two commonly detected environmental PBDE congeners, 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47) and 2,2′,4,4′,5-penta-bromodiphenyl ether (BDE-99), and their HO- and MeO- metabolites were considered in this study for their potential disrupting activity on thyroid hormone transport. Specifically, the study involved structural binding characterization of BDE-47 and BDE-99 including their two HO- and two MeO- metabolites with thyroxine-binding globulin (TBG), which is the main thyroid hormone transport protein in blood. The results showed that the binding pattern and molecular interactions of above two PBDEs and their metabolites exhibited overall similarity to native ligand, thyroxine in dock score, binding energy, and amino acid interactions with TBG. The BDE-99 and its metabolites were predicted to have stronger binding to TBG than BDE-47 with the metabolite 5-MeO-BDE-99 showing equal binding affinity to that of thyroxine. It is concluded that BDE-47 and BDE-99 and their metabolites have the potential to disrupt thyroid hormone transport and interfere in thyroid function. Keywords Endocrine disruption . Polybrominated diphenyl ethers . BDE-47 . BDE-99 . Structural binding simulation . Thyroxine-binding globulin

Introduction Polybrominated diphenyl ethers (PBDEs) are synthetic brominated flame retardants with extensive use in a range of consumer products, for instance, furniture, textiles, electric and electronic devices, etc., resulting in their bulk production (Alaee et al. 2003; Besis and Samara 2012). However, PBDEs leach out from commercial products due to their non-chemical Responsible Editor: Lotfi Aleya * Ishfaq Ahmad Sheikh [email protected] 1

King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia

2

Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

linkage with the polymer constituents during synthesis, use, dumping, and recycle processes of PBDEs (de