TY  - JOUR
A1  - Köhler, Yvonne
A1  - Luther, Eva Maria
A1  - Meyer, Sören
A1  - Schwerdtle, Tanja
A1  - Dringen, Ralf
T1  - Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes
JF  - Journal of trace elements in medicine and biology
N2  - Inorganic arsenicals are environmental toxins that have been connected with neuropathies and impaired cognitive functions. To investigate whether such substances accumulate in brain astrocytes and affect their viability and glutathione metabolism, we have exposed cultured primary astrocytes to arsenite or arsenate. Both arsenicals compromised the cell viability of astrocytes in a time- and concentration-dependent manner. However, the early onset of cell toxicity in arsenite-treated astrocytes revealed the higher toxic potential of arsenite compared with arsenate. The concentrations of arsenite and arsenate that caused within 24 h half-maximal release of the cytosolic enzyme lactate dehydrogenase were around 0.3 mM and 10 mM, respectively. The cellular arsenic contents of astrocytes increased rapidly upon exposure to arsenite or arsenate and reached after 4 h of incubation almost constant steady state levels. These levels were about 3-times higher in astrocytes that had been exposed to a given concentration of arsenite compared with the respective arsenate condition. Analysis of the intracellular arsenic species revealed that almost exclusively arsenite was present in viable astrocytes that had been exposed to either arsenate or arsenite. The emerging toxicity of arsenite 4 h after exposure was accompanied by a loss in cellular total glutathione and by an increase in the cellular glutathione disulfide content. These data suggest that the high arsenite content of astrocytes that had been exposed to inorganic arsenicals causes an increase in the ratio of glutathione disulfide to glutathione which contributes to the toxic potential of these substances.
KW  - Arsenic
KW  - Astrocytes
KW  - GSH
KW  - Metabolism
KW  - Toxicity
Y1  - 2014
U6  - https://doi.org/10.1016/j.jtemb.2014.04.007
SN  - 0946-672X
VL  - 28
IS  - 3
SP  - 328
EP  - 337
PB  - Elsevier
CY  - Jena
ER  -