# Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival.
> 高齢マウスのLPS誘発炎症モデルにおける2%水素ガス持続吸入による肺障害軽減効果


## Abstract

Against the backdrop of rising sepsis incidence in aging populations, this animal study examined the effects of hydrogen gas inhalation on LPS-induced systemic inflammation in 21–23-month-old male mice. Eight experimental groups were established, varying H2 concentration (1% or 2%) and exposure duration (1, 6, or 24 hours). Only the 24-hour 2% H2 inhalation regimen produced significant improvements: survival rates and locomotor activity increased, while mRNA levels of inflammatory markers in lung and liver tissue declined. Lung-specific senescence-associated molecules—including CXCL2, MMP-3, arginase-1, and the cell-cycle inhibitor p21—were also downregulated. Hepatic injury induced by LPS was not meaningfully altered under any tested condition. These findings indicate that prolonged, higher-concentration H2 inhalation selectively modulates pulmonary inflammation and aging-related molecular signatures in elderly mice.

### Mechanism

Continuous inhalation of 2% H2 for 24 hours suppressed mRNA expression of inflammatory cytokines and senescence-associated proteins (CXCL2, MMP-3, arginase-1, p21) in lung tissue, thereby reducing LPS-induced pulmonary injury in aged mice.

## Bibliographic

- **Authors**: Aokage T, Iketani M, Seya M, Meng Y, Ageta K, Naito H, et al.
- **Journal**: Exp Gerontol
- **Year**: 2023
- **PMID**: [37572992](https://pubmed.ncbi.nlm.nih.gov/37572992/)
- **DOI**: [10.1016/j.exger.2023.112270](https://doi.org/10.1016/j.exger.2023.112270)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: mixed
- **H2 concentration**: 1–2%

## 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 37572992. https://h2-papers.org/en/papers/37572992
> **Source**: PubMed PMID [37572992](https://pubmed.ncbi.nlm.nih.gov/37572992/)