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Effects of arsenolipids on in vitro blood-brain barrier model

Abstract

Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood–brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood–brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood–brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6 h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood–brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.

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Abbreviations

AsHC:

Arsenic-containing hydrocarbon

AsFA:

Arsenic-containing fatty acid

AsL:

Arsenolipid

DMAV :

Dimethylarsinic acid

iAsIII :

Arsenite

oxo-DMAPr:

Oxo-dimethylarsenopropanoic acid

PBCEC:

Porcine brain capillary endothelial cell

TEER:

Transendothelial electrical resistance

thio-DMAPr:

Thio-dimethylarsenopropanoic acid

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Acknowledgements

This work was supported by the Heinrich-Stockmeyer-Foundation, the German Research Foundation (DFG) Grant number SCHW903/10-1 and the Austrian Science Fund (FWF), Project number I2412-B21.

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Correspondence to T. Schwerdtle.

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Müller, S.M., Ebert, F., Raber, G. et al. Effects of arsenolipids on in vitro blood-brain barrier model. Arch Toxicol 92, 823–832 (2018). https://doi.org/10.1007/s00204-017-2085-8

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  • DOI: https://doi.org/10.1007/s00204-017-2085-8

Keywords

  • Arsenolipids
  • Arsenic-containing hydrocarbons
  • Arsenic-containing fatty acids
  • In vitro blood–brain barrier model