title: Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases.
abstract: BACKGROUND
  Sodium thiosulfate (STS) is an industrial chemical which has also been approved for the treatment of certain rare medical conditions. These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. Here, we investigated the anti-inflammatory activity of STS in our glial-mediated neuroinflammatory model.
  
  
  METHODS
  Firstly, we measured glutathione (GSH) and hydrogen sulfide (H2S, SH(-)) levels in glial cells after treatment with sodium hydrosulfide (NaSH) or STS. We also measured released levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) from them. We used two cell viability assays, MTT and lactate dehydrogenase (LDH) release assays, to investigate glial-mediated neurotoxicity and anti-inflammatory effects of NaSH or STS. We also employed Western blot to examine activation of intracellular inflammatory pathways.
  
  
  RESULTS
  We found that STS increases H2S and GSH expression in human microglia and astrocytes. When human microglia and astrocytes are activated by lipopolysaccharide (LPS)/interferon-γ (IFNγ) or IFNγ, they release materials that are toxic to differentiated SH-SY5Y cells. When the glial cells were treated with NaSH or STS, there was a significant enhancement of neuroprotection. The effect was concentration-dependent and incubation time-dependent. Such treatment reduced the release of TNFα and IL-6 and also attenuated activation of P38 MAPK and NFκB proteins. The compounds tested were not harmful when applied directly to all the cell types.
  
  
  CONCLUSIONS
  Although NaSH was somewhat more powerful than STS in these in vitro assays, STS has already been approved as an orally available treatment. STS may therefore be a candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component.
authors: Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. moonhee@mail.ubc.ca.
authors: Moonhee
authors: M
authors: Lee
authors: Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. mcgeer@mail.ubc.ca.
authors: Edith G
authors: EG
authors: McGeer
authors: Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. mcgeerpl@mail.ubc.ca.
authors: Patrick L
authors: PL
authors: McGeer
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000941:ethics; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008840:Microfilament Proteins; D009457:Neuroglia / Q000187:drug effects*; D013885:Thiosulfates / Q000494:pharmacology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C112986:AIF1 protein, human; D000975:Antioxidants; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D013885:Thiosulfates; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases; D006836:Hydro-Lyases; C045581:lactate dehydratase; C017717:sodium thiosulfate; D006862:Hydrogen Sulfide