Abstract
BackgroundSodium 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.MethodsFirstly, 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.ResultsWe 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.ConclusionsAlthough 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0488-8) contains supplementary material, which is available to authorized users.
Highlights
Sodium thiosulfate (STS) is an industrial chemical which has been approved for the treatment of certain rare medical conditions
We studied the effects of sodium hydrosulfide (NaSH) or Sodium thiosulfate anhydrous (STS) on SH-SY5Y neuronal cell death induced by supernatants from LPS and interferon-γ (IFNγ)-activated glial cells
We found that NaSH and STS generated H2S and GSH in THP-1 and U373 cells, reduced release of proinflammatory cytokines such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) from LPS/IFNγ-stimulated microglia and THP-1 cells, as well as IFNγ-stimulated astrocytes and U373 cells
Summary
Sodium thiosulfate (STS) is an industrial chemical which has been approved for the treatment of certain rare medical conditions These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. 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. Sodium thiosulphate (Na2S2O3, STS) is an industrial compound which is typically available as the pentahydrate, Na2S2O3 · 5H2O It has medical uses in the treatment of some rare medical conditions. These include calciphylaxis in hemodialysis patients with end-stage kidney disease [1] as well as cyanide poisoning [2]. STS is reported to protect neuronal cells from ischemia [6]
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