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1519021 
Journal Article 
Arsenate accumulation and arsenate-induced glutathione export in astrocyte-rich primary cultures 
Meyer, N; Koehler, Y; Tulpule, K; Dringen, R 
In Press 
Yes 
Neurochemistry International
ISSN: 0197-0186
EISSN: 1872-9754 
62 
1012-1019 
English 
Arsenate is a toxic compound that has been connected with neuropathies and impaired cognitive functions. To test whether arsenate affects the viability and the GSH metabolism of brain astrocytes, we have used primary astrocyte cultures as model system. Incubation of astrocytes for 2 h with arsenate in concentrations of up to 10 mM caused an almost linear increase in the cellular arsenic content, but did not acutely compromise cell viability. The presence of moderate concentrations of arsenate caused a time- and concentration-dependent loss of GSH from viable astrocytes which was accompanied by a matching increase in the extracellular GSH content. Half-maximal effects were observed for arsenate in a concentration of about 0.3 mM. The arsenate-induced stimulated GSH export from astrocytes was prevented by MK571, an inhibitor of the multidrug resistance protein 1. Exposure of astrocytes to arsenite increased the specific cellular arsenic content and stimulated GSH export to values that were similar to those observed for arsenate-treated cells, while dimethylarsinic acid was less efficiently accumulated by the cells and did not modulate cellular and extracellular GSH levels. The observed strong stimulation of GSH export from astrocytes by arsenate suggests that disturbances of the astrocytic GSH metabolism may contribute to the observed arsenic-induced neurotoxicity. 
Arsenic; Astrocytes; Export; GSH; Mrpl 
IRIS
• Arsenic Hazard ID
          ToxNet
          Considered New
          PubMed
          Considered New
          PubMed
          ToxNet
          Excluded
               Toxnet Duplicates
          PubMed
          ToxNet
          Excluded
               Toxnet Duplicates
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
     2. Lit Search Updates through Oct 2015
          PubMed
          WOS
          ToxNet
          Considered
     7. Other Studies through Oct 2015
          MOA
• Arsenic (Inorganic)
     1. Literature
          Lit search updates through Oct 2015
     3. Hazard ID Screening
          Other potentially supporting studies
     4. Adverse Outcome Pathways/Networks Screening
          Relevant
• Arsenic MOA
     4. Adverse Outcome Pathways
          Cell viability, cell proliferation, cell cycle changes (unrelated to regenerative proliferation)
          Oxidative stress related effects (includes non-specific SH reactions)
     5. Health Effect
          Nervous System Effects
     1. MOA Literature Screening
          Health Effect Screening