Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Institute of Chemistry-Analytical Chemistry, University of Graz, Universitaetsplatz 1, 8010, Graz, Austria.
Arch Toxicol. 2017 Sep;91(9):3121-3134. doi: 10.1007/s00204-017-1933-x. Epub 2017 Feb 8.
Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAs) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAs, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAs nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAs and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.
砷脂是脂溶性有机砷化合物，主要存在于海洋生物中，含砷烃 (AsHCs) 和含砷脂肪酸 (AsFAs) 是两个主要亚组。最近，对几种砷脂的毒性研究表明，这些砷脂对人肝和膀胱细胞具有很高的细胞毒性。此外，用黑腹果蝇进行的喂养研究表明，砷脂在果蝇的大脑中积累。在这项研究中，三种 AsHCs、两种 AsFAs 和三种代谢物（二甲砷酸、硫代/氧代-二甲基砷丙氨酸）的神经毒性潜力与毒性参考物质亚砷酸盐 (iAs) 在完全分化的人脑细胞 (LUHMES 细胞) 中进行了比较。在这种情况下，AsHCs 在低微摩尔浓度范围内降低了细胞数量和细胞活力，与 iAs 相当，而 AsFAs 和应用的代谢物毒性较低。机制研究表明，AsHCs 降低了线粒体膜电位，而 iAs 和 AsFAs 则没有影响。此外，通过检查神经元网络研究了神经毒性机制。在这里，AsHCs 严重扰乱了神经元网络并诱导了细胞凋亡作用，而 iAs 和 AsFAs 则显示出相对较小的作用。考虑到 AsHCs 在体外具有实质性的神经毒性潜力，并且它们可以穿过大脑的生理屏障，因此不能排除 AsHCs 在体内具有神经毒性潜力，需要紧急进行表征。
