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Effects of arsenolipids on in vitro blood-brain barrier model

  • 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 atArsenic-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.show moreshow less

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Author details:Sandra Marie MüllerORCiDGND, Franziska EbertORCiDGND, Georg RaberGND, Sören MeyerORCiDGND, Julia BornhorstORCiDGND, Stephan Hüwel, Hans-Joachim GallaORCiD, Kevin A. FrancesconiORCiD, Tanja SchwerdtleORCiDGND
ISSN:0340-5761
ISSN:1432-0738
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/29058019
Title of parent work (English):Archives of toxicology : official journal of EUROTOX
Publisher:Springer
Place of publishing:Heidelberg
Publication type:Article
Language:English
Date of first publication:2017/10/20
Publication year:2018
Release date:2022/02/03
Tag:Arsenic-containing fatty acids; Arsenic-containing hydrocarbons; Arsenolipids; In vitro blood-brain barrier model
Volume:92
Issue:2
Number of pages:10
First page:823
Last Page:832
Funding institution:Heinrich-Stockmeyer-Foundation; German Research Foundation (DFG)German Research Foundation (DFG) [SCHW903/10-1]; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [I2412-B21]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
DDC classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Peer review:Referiert
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