Sodium thiosulfate attenuates acute lung injury in Mice

Masahiro Sakaguchi, Eizo Marutani, Hae Sook Shin, Wei Chen, Kenjiro Hanaoka, Ming Xian, Fumito Ichinose

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

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-A. 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-êB 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.

Original languageEnglish
Pages (from-to)1248-1257
Number of pages10
JournalAnesthesiology
Volume121
Issue number6
DOIs
Publication statusPublished - 2014 Dec 4
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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