Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
Institute of Chemistry, NAWI Graz, University of Graz, Graz, Austria.
Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700199. Epub 2017 Aug 29.
In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids.
Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity.
These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment.
在一般人群中，砷的暴露主要通过饮食。海产品中的砷浓度最高，其中砷主要以有机形式存在，包括砷脂。由于最近的研究提供了证据表明砷脂可以到达生物体的大脑并在完全分化的人类神经元中发挥毒性，因此这项工作旨在评估砷脂的神经发育毒性。
在未分化的人神经元中，研究了三种含砷碳氢化合物 (AsHC)、两种含砷脂肪酸 (AsFA)、亚砷酸盐和二甲基砷酸 (DMA) 的神经发育效应。AsHC 和亚砷酸盐在相似的低浓度范围内引起明显的细胞毒性，而 AsFA 和 DMA 的毒性较小。AsHC 对细胞具有高度可及性，并表现出明显的神经发育效应，轴突生长和线粒体膜电位是敏感的终点；亚砷酸盐并没有显著降低这两个终点。在完全分化的神经元中，亚砷酸盐和 AsHC 引起轴突毒性。
这些结果表明 AsHC 具有神经发育潜力。考虑到在生命早期暴露时，AsHC 可能很容易到达发育中的大脑，因此不能排除神经毒性和神经发育毒性。需要进一步研究以推进迫切需要的风险评估。
