# Molecular hydrogen-mediated SIRT1 activation alleviates sepsis-associated encephalopathy by promoting mitophagy.
> 分子状水素によるSIRT1活性化が敗血症関連脳症においてミトファジーを促進することで神経保護効果を発揮する


## Abstract

A cecal ligation and puncture (CLP) mouse model of sepsis-associated encephalopathy (SAE) was used to examine the effects of 2% hydrogen gas inhalation. Seven-day survival improved from 50% to 75% (P < 0.01), and cognitive performance in the Morris water maze was enhanced, with increased platform crossings and shortened escape latency. Proteomic profiling combined with Western blotting, immunofluorescence, and electron microscopy revealed that hydrogen upregulated SIRT1 expression and activated PINK1/Parkin-dependent mitophagy. Downstream consequences included reduced STING phosphorylation, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and diminished neuronal apoptosis in the hippocampal CA1 region. Administration of the SIRT1 inhibitor EX527 abolished these protective outcomes, confirming that SIRT1-mediated mitophagy is the central mechanism through which hydrogen mitigates neuroinflammation and neuronal loss in SAE.

### Mechanism

Hydrogen activates SIRT1, which promotes PINK1/Parkin-dependent mitophagy, leading to suppressed STING phosphorylation, reduced pro-inflammatory cytokine production (IL-1β, IL-6, TNF-α), and decreased neuronal apoptosis in the hippocampal CA1 region.

## Bibliographic

- **Authors**: Meng S, Wang Z, Fan Y, Pei S, Cui J, Liu J, et al.
- **Journal**: Eur J Med Res
- **Year**: 2025 (2025-12-05)
- **PMID**: [41351127](https://pubmed.ncbi.nlm.nih.gov/41351127/)
- **DOI**: [10.1186/s40001-025-03600-5](https://doi.org/10.1186/s40001-025-03600-5)
- **PMC**: [PMC12829070](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829070/)
- **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 41351127. https://h2-papers.org/en/papers/41351127
> **Source**: PubMed PMID [41351127](https://pubmed.ncbi.nlm.nih.gov/41351127/)