Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Heinrich-Stockmeyer Foundation, Parkstraße 44-46, 49214, Bad Rothenfelde, Germany.
Arch Toxicol. 2018 Feb;92(2):823-832. doi: 10.1007/s00204-017-2085-8. Epub 2017 Oct 20.
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 (iAs). 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.
含砷烃（AsHCs）是鱼和可食用藻类中砷脂（AsLs）的一个亚组，在完全分化的人脑细胞中具有很大的神经毒性潜力。先前的体内研究表明，AsHCs 可穿过果蝇的血脑屏障，这引发了一个问题，即 AsLs 是否也可以穿过脊椎动物的血脑屏障（BBB）。在本研究中，我们研究了几种 AsLs（AsHC 332、AsHC 360、AsHC 444 以及两种含砷脂肪酸 AsFA 362 和 AsFA 388）及其代谢物（硫/氧-二甲基丙酸、二甲基砷酸）对猪脑毛细血管内皮细胞（PBCECs，血脑屏障的体外模型）的影响。AsHCs 表现出所有研究的砷化合物中最强的细胞毒性作用，其效力比有毒参考物质亚砷酸盐（iAs）高出五倍。在我们的体外 BBB 模型中，我们观察到在不影响屏障完整性的浓度下，AsHC 332 在 6 小时后有轻微的穿透 BBB。此外，在亚细胞毒性浓度下孵育 AsHCs 会导致屏障破坏。随后对三种紧密连接蛋白的免疫细胞化学染色显示对细胞膜有重大影响。由于 AsHCs 增加了体外血脑屏障的通透性，因此不能排除在体内系统中也存在类似的行为。因此，AsHCs 可能有助于伴随食物源毒物转移到大脑中。
