Journal article
Sodium thiosulfate attenuates acute lung injury in mice
Anesthesiology (Philadelphia), Vol.121(6), pp.1248-1257
12/2014
Handle:
https://hdl.handle.net/2376/110790
PMCID: PMC4237715
PMID: 25260144
Abstract
Acute lung injury is characterized by neutrophilic inflammation and increased lung permeability. Thiosulfate is a stable metabolite of hydrogen sulfide, a gaseous mediator that exerts antiinflammatory effects. Although sodium thiosulfate (STS) has been used as an antidote, the effect of STS on acute lung injury is unknown. The authors assessed the effects of STS on mice lung and vascular endothelial cells subjected to acute inflammation.
Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide or subjected to cecal ligation and puncture with or without STS. Effects of STS on endothelial permeability and the production of inflammatory cytokines and reactive oxygen species were examined in cultured endothelial cells incubated with lipopolysaccharide or tumor necrosis factor-α. Levels of sulfide and sulfane sulfur were measured using novel fluorescence probes.
STS inhibited lipopolysaccharide-induced production of cytokines (interleukin-6 [pg/ml]; 313±164, lipopolysaccharide; 79±27, lipopolysaccharide+STS [n=10]), lung permeability, histologic lung injury, and nuclear factor-κB activation in the lung. STS also prevented up-regulation of interleukin-6 in the mouse lung subjected to cecal ligation and puncture. In endothelial cells, STS increased intracellular levels of sulfide and sulfane sulfur and inhibited lipopolysaccharide or tumor necrosis factor-α-induced production of cytokines and reactive oxygen species. The beneficial effects of STS were associated with attenuation of the lipopolysaccharide-induced nuclear factor-κB activation through the inhibition of tumor necrosis factor receptor-associated factor 6 ubiquitination.
STS exerts robust antiinflammatory effects in mice lung and vascular endothelium. The results suggest a therapeutic potential of STS in acute lung injury.
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Details
- Title
- Sodium thiosulfate attenuates acute lung injury in mice
- Creators
- Masahiro Sakaguchi - From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (M.S., E.M., H.-s.S., F.I.); Department of Chemistry, Washington State University, Pullman, Washington (W.C., M.X.); and Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan (K.H.)Eizo MarutaniHae-sook ShinWei ChenKenjiro HanaokaMing XianFumito Ichinose
- Publication Details
- Anesthesiology (Philadelphia), Vol.121(6), pp.1248-1257
- Academic Unit
- Chemistry, Department of
- Publisher
- United States
- Grant note
- R01 HL101930 / NHLBI NIH HHS R01HL101930 / NHLBI NIH HHS
- Identifiers
- 99900547108301842
- Language
- English
- Resource Type
- Journal article