Inhaled hydrogen sulfide prevents endotoxin-induced systemic inflammation and improves survival by altering sulfide metabolism in mice

Kentaro Tokuda, Kotaro Kida, Eizo Marutani, Ettore Crimi, Masahiko Bougaki, Ashok Khatri, Hideo Kimura, Fumito Ichinose

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


Aims: The role of hydrogen sulfide (H2S) in endotoxin (lipopolysaccharide [LPS])-induced inflammation is incompletely understood. We examined the impact of H2S breathing on LPS-induced changes in sulfide metabolism, systemic inflammation, and survival in mice. Results: Mice that breathed air alone exhibited decreased plasma sulfide levels and poor survival rate at 72 h after LPS challenge. Endotoxemia markedly increased alanine aminotransferase (ALT) activity and nitrite/nitrate (NOx) levels in plasma and lung myeloperoxidase (MPO) activity in mice that breathed air. In contrast, breathing air supplemented with 80 ppm of H2S for 6 h after LPS challenge markedly improved survival rate compared to mice that breathed air alone (p<0.05). H2S breathing attenuated LPS-induced increase of plasma ALT activity and NOx levels and lung MPO activity. Inhaled H 2S suppressed LPS-induced upregulation of inflammatory cytokines, while it markedly induced anti-inflammatory interleukin (IL)-10 in the liver. Beneficial effects of H2S inhalation after LPS challenge were associated with restored sulfide levels and markedly increased thiosulfate levels in plasma. Increased thiosulfate levels after LPS challenge were associated with upregulation of rhodanese, but not cystathionine-γ-lyase (CSE), in the liver. Administration of sodium thiosulfate dose-dependently improved survival after LPS challenge in mice. Innovation: By measuring changes in plasma levels of sulfide and sulfide metabolites using an advanced analytical method, this study revealed a critical role of thiosulfate in the protective effects of H2S breathing during endotoxemia. Conclusion: These observations suggest that H2S breathing prevents inflammation and improves survival after LPS challenge by altering sulfide metabolism in mice.

Original languageEnglish
Pages (from-to)11-21
Number of pages11
JournalAntioxidants and Redox Signaling
Issue number1
Publication statusPublished - Jul 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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