# Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway.
> 敗血症マウスの肺組織におけるHMGB1放出に対する水素ガスの抑制効果：Nrf2/HO-1経路を介したメカニズムの検討


## Abstract

Using a cecal ligation and puncture (CLP) sepsis model in wild-type and Nrf2-knockout ICR mice, the effects of 2% H2 gas inhalation (60 min at 1 h and 6 h post-surgery) on lung injury were examined. In wild-type animals, H2 inhalation improved 7-day survival, reduced the lung wet/dry weight ratio and histopathological injury scores, lowered pro-inflammatory mediators (TNF-α, IL-6, HMGB1), elevated the anti-inflammatory cytokine IL-10, enhanced antioxidant enzymes (SOD, CAT, HO-1), and decreased the oxidative marker MDA. These protective outcomes were absent in Nrf2-knockout mice, indicating that Nrf2 is essential for H2-mediated upregulation of HO-1 and downregulation of HMGB1, thereby attenuating sepsis-induced pulmonary damage.

### Mechanism

H2 gas activates Nrf2, which upregulates HO-1 expression and suppresses HMGB1 release, leading to reduced oxidative stress and pro-inflammatory cytokine levels that collectively mitigate sepsis-induced lung injury.

## Bibliographic

- **Authors**: Yang Y, Yang M, Wang CY, Xie K, Yu Y
- **Journal**: Int Immunopharmacol
- **Year**: 2019
- **PMID**: [30660872](https://pubmed.ncbi.nlm.nih.gov/30660872/)
- **DOI**: [10.1016/j.intimp.2019.01.022](https://doi.org/10.1016/j.intimp.2019.01.022)
- **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 30660872. https://h2-papers.org/en/papers/30660872
> **Source**: PubMed PMID [30660872](https://pubmed.ncbi.nlm.nih.gov/30660872/)