TY  - JOUR
A1  - Witt, Barbara
A1  - Ebert, Franziska
A1  - Meyer, Sören
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - Scope: 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. Methods and results: Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA(V)) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA(V) 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. Conclusion: 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.
KW  - Arsenic-containing fatty acids
KW  - Arsenic-containing hydrocarbons
KW  - Arsenite
KW  - Arsenolipids
KW  - Neurodevelopmental toxicity
Y1  - 2017
U6  - https://doi.org/10.1002/mnfr.201700199
SN  - 1613-4125
SN  - 1613-4133
VL  - 61
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Witt, Barbara
A1  - Meyer, Sören
A1  - Ebert, Franziska
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons
JF  - Archives of toxicology : official journal of EUROTOX
N2  - 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 (iAsIII) 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 iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII 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 iAsIII 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.
KW  - Arsenolipids
KW  - Neurons
KW  - Cytotoxicity
KW  - Neurotoxicity
KW  - Arsenic-containing hydrocarbons
KW  - Arsenic-containing fatty acids
Y1  - 2017
U6  - https://doi.org/10.1007/s00204-017-1933-x
SN  - 0340-5761
SN  - 1432-0738
VL  - 91
SP  - 3121
EP  - 3134
PB  - Springer
CY  - Heidelberg
ER  -