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  - 
TY  - JOUR
A1  - Lohren, Hanna
A1  - Blagojevic, Lara
A1  - Fitkau, Romy
A1  - Ebert, Franziska
A1  - Schildknecht, Stefan
A1  - Leist, Marcel
A1  - Schwerdtle, Tanja
T1  - Toxicity of organic and inorganic mercury species in human neurons and human astrocytes
JF  - Journal of trace elements in medicine and biology
N2  - Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.
KW  - Methylmercury
KW  - Thiomersal
KW  - Mercuric mercury
KW  - Human differentiated neurons
KW  - Cytotoxicity
KW  - Apoptosis
Y1  - 2015
U6  - https://doi.org/10.1016/j.jtemb.2015.06.008
SN  - 0946-672X
VL  - 32
SP  - 200
EP  - 208
PB  - Elsevier
CY  - Jena
ER  -