title: Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes.
abstract: 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 24h half-maximal release of the cytosolic enzyme lactate dehydrogenase were around 0.3mM and 10mM, respectively. The cellular arsenic contents of astrocytes increased rapidly upon exposure to arsenite or arsenate and reached after 4h 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 4h 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.
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Centre for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Koehler
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Centre for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Luther
authors.affiliation: Graduate School of Chemistry, University of Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany; Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
authors.forename: Soeren
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.affiliation: Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany; Centre for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany. Electronic address: ralf.dringen@uni-bremen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dringen
mesh_terms: D000818:Animals; D001149:Arsenates / Q000378:metabolism / Q000633:toxicity*; D018053:Arsenites / Q000378:metabolism / Q000633:toxicity*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001149:Arsenates; D018053:Arsenites; C015001:arsenite; C025657:arsenic acid
keywords: Arsenic; Astrocytes; GSH; Metabolism; Toxicity