# Combination therapy with molecular hydrogen and hyperoxia in a murine model of polymicrobial sepsis.
> 多菌性敗血症マウスモデルにおける水素ガスと高濃度酸素の併用効果


## Abstract

Using a cecal ligation and puncture (CLP) murine sepsis model, this study examined the effects of 2% H2 inhalation, 98% hyperoxia, and their combination. In moderate CLP mice, each intervention alone raised 14-day survival from 40% to 80% or 70%, respectively, while the combined approach achieved 100% survival. In severe CLP, 7-day survival improved from 0% to 70% with combination. Organ injury markers in lung, liver, and kidney were reduced, accompanied by lower oxidative stress indicators (8-iso-prostaglandin F2α) and pro-inflammatory cytokines (HMGB1, TNF-α), alongside elevated antioxidant enzyme activities (superoxide dismutase, catalase) and the anti-inflammatory cytokine interleukin-10. These findings indicate that concurrent H2 and hyperoxia administration produces additive protective effects through both antioxidant and anti-inflammatory mechanisms.

### Mechanism

H2 selectively scavenges reactive oxygen species, reducing oxidative stress markers. Combined with hyperoxia, it further elevates superoxide dismutase and catalase activities while suppressing pro-inflammatory mediators HMGB1 and TNF-α and increasing IL-10, resulting in enhanced multi-organ protection.

## Bibliographic

- **Authors**: Xie K, Fu W, Xing W, Li A, Chen H, Han H, et al.
- **Journal**: Shock
- **Year**: 2012
- **PMID**: [23160520](https://pubmed.ncbi.nlm.nih.gov/23160520/)
- **DOI**: [10.1097/SHK.0b013e3182758646](https://doi.org/10.1097/SHK.0b013e3182758646)
- **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 23160520. https://h2-papers.org/en/papers/23160520
> **Source**: PubMed PMID [23160520](https://pubmed.ncbi.nlm.nih.gov/23160520/)