title: Sodium thiosulfate attenuates acute lung injury in mice.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  STS exerts robust antiinflammatory effects in mice lung and vascular endothelium. The results suggest a therapeutic potential of STS in acute lung injury.
authors.affiliation: 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.).
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Eizo
authors.initials: E
authors.lastname: Marutani
authors.forename: Hae-sook
authors.initials: HS
authors.lastname: Shin
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002432:Cecum / Q000293:injuries; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013885:Thiosulfates / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013885:Thiosulfates; C017717:sodium thiosulfate