TY  - JOUR
A1  - Müller, Sandra Marie
A1  - Ebert, Franziska
A1  - Bornhorst, Julia
A1  - Galla, Hans-Joachim
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier
JF  - Journal of trace elements in medicine and biology
N2  - Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health. In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.
KW  - Arsenolipids
KW  - Blood-liquor barrier
KW  - Blood-cerebrospinal fluid barrier
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
Y1  - 2018
U6  - https://doi.org/10.1016/j.jtemb.2018.01.020
SN  - 0946-672X
VL  - 49
SP  - 171
EP  - 177
PB  - Elsevier GMBH
CY  - München
ER  - 
TY  - JOUR
A1  - Müller, Sandra Marie
A1  - Ebert, Franziska
A1  - Raber, Georg
A1  - Meyer, Sören
A1  - Bornhorst, Julia
A1  - Hüwel, Stephan
A1  - Galla, Hans-Joachim
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Effects of arsenolipids on in vitro blood-brain barrier model
JF  - Archives of toxicology : official journal of EUROTOX
N2  - 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.
KW  - Arsenolipids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
KW  - In vitro blood-brain barrier model
Y1  - 2017
SN  - 0340-5761
SN  - 1432-0738
VL  - 92
IS  - 2
SP  - 823
EP  - 832
PB  - Springer
CY  - Heidelberg
ER  -