Pentabromoethylbenzene Exposure Induces Transcriptome Aberration and Thyroid Dysfunction: In Vitro, in Silico, and in Vivo Investigations

Abstract

Pentabromoethylbenzene (PBEB), as one of the novel brominated flame retardants (NFBRs), has caused increasing public concern for health risks. Till now, information regarding potential effects of PBEB on thyroid function remains unclear. Herein, we investigated thyroid disruption of PBEB in vitro and in silico and evaluated thyroid dysfunction induced by PBEB using Sprague–Dawley rats. PBEB showed thyroid receptor (TR) β antagonistic activity with IC50 of 9.82 × 10–7 M in the dual-luciferase reporter gene assay and induced relative reorientation of helix 11 (H11) and H12 of the TR ligand binding domain as revealed by molecular dynamics simulations. PBEB (0.2, 2, 20 mg/kg BW/d) markedly altered the transcriptome profile of thyroid with induction of 17, 42, and 119 differentially expressed genes (DEGs) involved in thyroid hormone signaling and synthesis pathway, of which transthyretin and albumin are common DEGs. The 28-d exposure to PBEB significantly decreased the triiodothyronine level (from 7.23 to 5.67 ng/mL) and increased the thyrotropin level (from 7.88 to 12.86 mU/L) for female rats. PBEB consequently reduced thyroid weight and altered its morphology with more depleted follicles. Overall, our study provides the first account of evidence on PBEB exerted thyroid disruption, transcriptome aberration, and morphological alteration, facilitating health risk assessment of PBEB and structurally related NBFRs.

IsPETase- and IsMHETase-Catalyzed Cascade Degradation Mechanism toward Polyethylene Terephthalate

“…60 Na + was used to neutralize the charge of the system. 61 The temperature of the whole system was increased from 0 to 298.15 K in 50 ps and then the thermal equilibrium state was reached in about 500 ps (1 fs per step). Afterward the random boundary molecular dynamics simulation was carried out at 298.15 K using the NVT system for conformation sampling.…”

“…The missing hydrogen atoms in the crystal structure were added by using the HBUILD module in the CHARMM package. , The TIP3P water model was used to dissolve the complex system of the enzyme with a radius of 30 Å . Na + was used to neutralize the charge of the system . The temperature of the whole system was increased from 0 to 298.15 K in 50 ps and then the thermal equilibrium state was reached in about 500 ps (1 fs per step).…”

Enhanced Disrupting Effect of Benzophenone-1 Chlorination Byproducts to the Androgen Receptor: Cell-Based Assays and Gaussian Accelerated Molecular Dynamics Simulations

“…These structures served as protein templates for the molecular docking of BP-1 and chlorinated products (texts S6 and S7). The post-GaMD analysis and binding free energy via MMGBSA calculation , are described in text S8.…”

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“…Jeong et al developed AOPs using mammalian toxicity data obtained from ToxCast . Molecular dynamic (MD) simulation, an in silico techniques, can also be utilized to identify the MIEs in AOPs to directly relate chemical properties to activities. ,,− The previous study also successfully applied this approach to reveal the crucial role of C terminal H12 in the molecular interaction of bisphenol S (BPS) toward the thyroid hormone receptor β (TRβ) . As described above, the computational approach can identify useful biological data from public data sources to elucidate the unknown mechanisms of chemical toxicity .…”