The Rev. W Awdry might have been all too right with his use of the name "The Diseasel".
This paper suggests specific effects of diesel exhaust on thyroid receptor alpha - but needing more research (as always!)
Surprisingly, it appears that some constituents enhance the effect of our own T3!
Sci Total Environ. 2019 Apr 27;677:626-636. doi: 10.1016/j.scitotenv.2019.04.390. [Epub ahead of print]
Modulation of endocrine nuclear receptor activities by polyaromatic compounds present in fractionated extracts of diesel exhaust particles.
Pěnčíková K1, Ciganek M1, Neča J1, Illés P2, Dvořák Z2, Vondráček J3, Machala M4.
Author information
1 Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
2 Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Šlechtitelů 27, 783 71 Olomouc, Czech Republic.
3 Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech Republic.
4 Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic. Electronic address: machala@vri.cz.
Abstract
Organic pollutants associated with diesel exhaust particles (DEP), such as polycyclic aromatic hydrocarbons (PAHs) and their derivatives, may negatively impact human health. However, a comprehensive overview of their effects on endocrine nuclear receptor activities is still missing. Here, we evaluated the effects of extracts and chromatographic fractions (fractionated according to increasing polarity) of two standard reference materials derived from distinct types of diesel engines (SRM 2975, SRM 1650b), on activation of androgen receptor (AR), estrogen receptor alpha (ERα), peroxisome proliferator-activated receptor γ (PPARγ), glucocorticoid receptor (GR) and thyroid receptor α (TRα), using human cell-based reporter gene assays. Neither DEP standard modulated AR or GR activities. Crude extracts and fractions of SRM 1650b and SRM 2975 suppressed ERα-mediated activity in the ER-CALUX™ assay; however, this effect could be partly linked to their cytotoxicity in this cell line. We observed that only SRM 2975 extract and its fractions were partial PPARγ inducers, while SRM 1650b extract was not active towards this receptor. Importantly, we found that both extracts and polar fractions of SRM activated TRα and significantly potentiated the activity of endogenous TRα ligand, triiodothyronine. Based on a detailed chemical analysis of both extracts and their polar fractions, we identified several oxygenated PAH derivatives, that were present at relatively high levels in the analyzed DEP standards, including 3-nitrobenzanthrone (3-NBA), anthracene-9,10-dione, phenanthrene-9,10-dione, 9H-fluoren-9-one or benzo[a]anthracene-7,12-dione, to activate TRα activity. Nevertheless, these compounds provided only a minor contribution to the overall TRα activity identified in polar fractions. This suggests that yet unidentified polar polyaromatic compounds associated with DEP may, apart from their known impact on the aryl hydrocarbon receptor or steroid signaling, deregulate activities of additional nuclear receptors, in particular of TRα. This illustrates the need to better characterize endocrine disrupting activities of DEP.
Copyright © 2019 Elsevier B.V. All rights reserved.
KEYWORDS:
Androgen receptor; Diesel exhaust particles; Estrogen receptor α; Glucocorticoid receptor; Peroxisome proliferator-activated receptor γ; Thyroid receptor α
PMID: 31071665
DOI: 10.1016/j.scitotenv.2019.04.390
