Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons

作者: Barbara Witt , Sören Meyer , Franziska Ebert , Kevin A. Francesconi , Tanja Schwerdtle

DOI: 10.1007/S00204-017-1933-X

关键词:

摘要: Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential those human liver bladder cells. Furthermore, feeding Drosophila melanogaster indicated an accumulation the fruit fly’s brain. In this study, neurotoxic three AsHCs, AsFAs metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated comparison to toxic reference arsenite (iAsIII) fully differentiated brain cells (LUHMES cells). Thereby, case AsHCs both cell number viability were reduced low micromolar concentration range comparable iAsIII, while applied less toxic. Mechanistic revealed that mitochondrial membrane potential, whereas neither iAsIII nor had impact. mechanisms by examining neuronal network. Here, massively disturbed network induced apoptotic effects, comparatively lesser effects. Taking into account substantial vitro fact they could transfer across physiological barriers brain, vivo for cannot be excluded needs urgently characterized.

参考文章(53)
Hanna Lohren, Lara Blagojevic, Romy Fitkau, Franziska Ebert, Stefan Schildknecht, Marcel Leist, Tanja Schwerdtle, Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes Journal of Trace Elements in Medicine and Biology. ,vol. 32, pp. 200- 208 ,(2015) , 10.1016/J.JTEMB.2015.06.008
Sören Meyer, Georg Raber, Franziska Ebert, Mojtaba S Taleshi, Kevin A Francesconi, Tanja Schwerdtle, Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model Molecular Nutrition & Food Research. ,vol. 59, pp. 2044- 2056 ,(2015) , 10.1002/MNFR.201500286
Diana Scholz, Dominik Pöltl, Andreas Genewsky, Matthias Weng, Tanja Waldmann, Stefan Schildknecht, Marcel Leist, Rapid, complete and large‐scale generation of post‐mitotic neurons from the human LUHMES cell line Journal of Neurochemistry. ,vol. 119, pp. 957- 971 ,(2011) , 10.1111/J.1471-4159.2011.07255.X
S. Meyer, G. Raber, F. Ebert, L. Leffers, S. M. Müller, M. S. Taleshi, K. A. Francesconi, T. Schwerdtle, In vitro toxicological characterisation of arsenic-containing fatty acids and three of their metabolites Toxicology Research. ,vol. 4, pp. 1289- 1296 ,(2015) , 10.1039/C5TX00122F
Chien-Te Chou, Hong-Ting Lin, Pai-An Hwang, Shang-Ta Wang, Cheng-Hong Hsieh, Deng-Fwu Hwang, Taurine resumed neuronal differentiation in arsenite-treated N2a cells through reducing oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction Amino Acids. ,vol. 47, pp. 735- 744 ,(2015) , 10.1007/S00726-014-1901-1
Sukumar Chattopadhyay, Sraboni Bhaumik, Aditi Nag Chaudhury, Shyamal Das Gupta, Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture. Toxicology Letters. ,vol. 128, pp. 73- 84 ,(2002) , 10.1016/S0378-4274(01)00535-5
Uk Namgung, Zhengui Xia, Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and p38 MAP kinases. Toxicology and Applied Pharmacology. ,vol. 174, pp. 130- 138 ,(2001) , 10.1006/TAAP.2001.9200
Julie Lotharius, Jeppe Falsig, Johan van Beek, Sarah Payne, Ralf Dringen, Patrik Brundin, Marcel Leist, Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase pathway. The Journal of Neuroscience. ,vol. 25, pp. 6329- 6342 ,(2005) , 10.1523/JNEUROSCI.1746-05.2005
Anne K. Krug, Nina V. Balmer, Florian Matt, Felix Schönenberger, Dorit Merhof, Marcel Leist, Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants Archives of Toxicology. ,vol. 87, pp. 2215- 2231 ,(2013) , 10.1007/S00204-013-1072-Y
S. Meyer, J. Schulz, A. Jeibmann, M. S. Taleshi, F. Ebert, K. A. Francesconi, T. Schwerdtle, Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster Metallomics. ,vol. 6, pp. 2010- 2014 ,(2014) , 10.1039/C4MT00249K