# Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release.
> 水素ガス吸入による多菌性敗血症マウスモデルへの保護効果：酸化ストレスおよびHMGB1放出の抑制を介したメカニズム


## Abstract

Sepsis remains a leading cause of mortality in intensive care settings, with excessive reactive oxygen species production central to its pathophysiology. Using a cecal ligation and puncture (CLP) mouse model, this study examined whether H2 gas inhalation could confer protection against sepsis-related organ damage. Inhalation of 2% H2 initiated at 1 or 6 hours post-CLP significantly improved survival in both moderate and severe CLP groups, with effects dependent on concentration and timing. Multiple organ injury markers—including lung myeloperoxidase activity, wet-to-dry weight ratio, bronchoalveolar lavage protein levels, serum biochemical parameters, and histopathological scores—were substantially reduced by H2 inhalation at 24 hours post-CLP. Mechanistically, H2 exposure was associated with decreased oxidative product levels, elevated antioxidant enzyme activities, and lower concentrations of high-mobility group box 1 (HMGB1) in both serum and tissue. These findings suggest that H2 inhalation may offer a protective approach against sepsis-induced organ dysfunction.

### Mechanism

H2 selectively scavenges hydroxyl radicals, reducing oxidative damage while enhancing antioxidant enzyme activity. Concurrently, it suppresses the release of HMGB1, a late-phase inflammatory mediator, thereby limiting multi-organ injury in sepsis.

## Bibliographic

- **Authors**: Xie K, Yu Y, Pei Y, Hou L, Chen SL, Xiong L, et al.
- **Journal**: Shock
- **Year**: 2010
- **PMID**: [19997046](https://pubmed.ncbi.nlm.nih.gov/19997046/)
- **DOI**: [10.1097/SHK.0b013e3181cdc4ae](https://doi.org/10.1097/SHK.0b013e3181cdc4ae)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 19997046. https://h2-papers.org/en/papers/19997046
> **Source**: PubMed PMID [19997046](https://pubmed.ncbi.nlm.nih.gov/19997046/)