Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier

[helvella]

Obviously we want fire-resistant furniture and electrical goods. Trouble seems to be that how we achieve those goals could be having a plethora of effects on us.

Toxicol Sci. 2019 Mar 4. pii: kfz059. doi: 10.1093/toxsci/kfz059. [Epub ahead of print]

Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier.

Cannon RE1, Trexler AW1, Knudsen GA1, Evans RA2, Birnbaum LS1.

Author information

1 Laboratory of Toxicology and Toxicokinetics, National Cancer Institute, National Institutes of Health, Research Triangle Park, NC, USA.

2 University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Abstract

Tetrabromobisphenol A (TBBPA, CAS No. 79-94-7) is a brominated flame retardant (BFR) used in 90% of epoxy coated circuit boards. Exposures to TBBPA can induce neurotoxicity, and disrupt MAPK, estrogen, thyroid, and PPAR-associated signaling pathways [1-5]. Since these pathways also regulate transporters of the central nervous system (CNS) barriers [6-9], we sought to determine the effect of TBBPA on the expression and activity of three ABC transporters of the blood-brain barrier (BBB). Using a confocal based assay, we measured the ex vivo and in vivo effects of TBBPA on P-glycoprotein (P-gp), Breast Cancer Resistant Protein (BCRP), and Multidrug Resistance-associated Protein 2 (MRP2) transport activity in rat brain capillaries. Our rationale for using a rat model was based on tissue availability, ease of handling, and availability of historical TBBPA toxicokinetic data. We found that TBBPA (1-1000 nM) exposure had no significant effect on MRP2 transport activity in either sex, suggesting TBBPA does not compromise the physical integrity of the BBB. However, low concentrations of TBBPA (1-100 nM) significantly decreased BCRP transport activity in both sexes. Additionally, TBBPA exposures (1-100 nM), elicited a sex-dependent response in P-gp transport: increasing transport activity in males and decreasing transport activity in females. All TBBPA dependent changes in transport activity were dose- and time-dependent. Inhibitors of either transcription or translation abolished the TBBPA dependent increases in male P-gp transport activity. Western blot and immuno-fluorescent assays confirmed the TBBPA dependent P-gp increases in males and decreases in females. Antagonizing PPAR-γ abolished the TBBPA dependent increases in males but not the decreases in females. However, the decreases in female P-gp transport were blocked by an ER-α antagonist. This work indicates that environmentally relevant concentrations of TBBPA (1-100 nM) alter ABC transporter function at the blood-brain barrier. Moreover, permeability changes in the blood-brain barrier can alter brain homeostasis, hinder CNS drug delivery, and increase the brain's exposure to harmful xenobiotic toxicants.

Published by Oxford University Press 2019.

KEYWORDS:

ABC transporters; Blood-brain Barrier; Brominated Flame Retardants; Estrogen Receptor Alpha; P-glycoprotein; PPAR gamma; Tetrabromobisphenol A

PMID: 30830211

DOI: 10.1093/toxsci/kfz059

ncbi.nlm.nih.gov/pubmed/308...

For those of you who are not familiar with ABC transporters (which definitely includes me), this document has quite a bit of information and includes some nice pictures to help!

pcp.nihtraining.com/handout...

[nightingale-56]

With hindsight and the knowledge of posts such as this, it makes me wish I had never taken up curtain and soft furnishing as an alternative career when I left work to have children. Thanks for posting this though helvella .