Uptake and toxicity of arsenite and arsenate in cultured brain astrocytes |
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| Affiliation: | 1. Centre for Biomolecular Interactions Bremen, Faculty 2 (Biology/Chemistry), University of Bremen, PO Box 330440, D-28334 Bremen, Germany;2. Centre for Environmental Research and Sustainable Technology, Leobener Strasse, D-28359 Bremen, Germany;3. Graduate School of Chemistry, University of Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany;4. Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany;1. Department of Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India;2. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India;3. From the Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892 and;4. the Department of Pathology, Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461;1. Sutcuimam University, Faculty of Medicine, Department of Dermatology, Kahramanmaras, Turkey;2. Sutcuimam University, Faculty of Medicine, Department of Biochemistry, Kahramanmaras, Turkey;3. Konya Education Research Hospital, Department of Dermatology, Konya, Turkey;4. Fatih University, Faculty of Medicine, Department of Anatomy, Istanbul, Turkey;5. Mersin University, Faculty of Medicine, Department of Biochemistry, Mersin, Turkey;6. Gaziantep University, Faculty of Medicine, Department of Dermatology, Turkey;1. Department of Analytical Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland;2. Outpatients Clinic for Drug Prevention and Treatment of Addicts, Św. Katarzyny 3, 31-063 Krakow, Poland;3. Laboratory of Analytical Toxicology and Therapeutic Drug Monitoring, Faculty of Medicine Jagiellonian University, Kopernika 15b, 31-501 Krakow, Poland;4. Laboratory of High Resolution Mass Spectrometry, Regional Laboratory of Physicochemical Analysis and Structural Research, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland;1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA;2. Hawaii Institute of Marine Biology, University of Hawaii, Kaneohe, HI 96744, USA |
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| 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 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. |
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| Keywords: | Arsenic Astrocytes GSH Metabolism Toxicity |
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