# Hydrogen restores central tryptophan and metabolite levels and maintains mitochondrial homeostasis to protect rats from chronic mild unpredictable stress damage.
> 水素吸入が慢性軽度予測不能ストレスラットにおけるトリプトファン代謝および脳内ミトコンドリア恒常性に与える影響


## Abstract

Forty Sprague-Dawley rats were randomly assigned to control, CUMS model, hydrogen inhalation, or positive drug groups. Following four weeks of stress modeling, 2–4% hydrogen gas was administered by inhalation. Behavioral tests, biochemical assays, and immunohistochemical analyses revealed that hydrogen inhalation reduced depressive-like behaviors and attenuated hippocampal neuronal injury in CUMS-exposed animals. Levels of monoamine neurotransmitters, tryptophan and its metabolites, inflammatory cytokines, and oxidative stress markers were restored toward control values. Additionally, mitochondrial homeostasis was preserved, accompanied by upregulation of PGC-1α, PINK1, and Parkin expression, suggesting activation of mitochondrial biogenesis and mitophagy pathways.

### Mechanism

Hydrogen upregulates PGC-1α, PINK1, and Parkin to promote mitochondrial biogenesis and mitophagy, while simultaneously reducing oxidative stress and neuroinflammation, thereby protecting hippocampal neurons in CUMS-exposed rats.

## Bibliographic

- **Authors**: Li J, Hao G, Yan Y, Li M, Li G, Lu Z, et al.
- **Journal**: Neurochem Int
- **Year**: 2025
- **PMID**: [39653185](https://pubmed.ncbi.nlm.nih.gov/39653185/)
- **DOI**: [10.1016/j.neuint.2024.105914](https://doi.org/10.1016/j.neuint.2024.105914)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2–4%

## 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 39653185. https://h2-papers.org/en/papers/39653185
> **Source**: PubMed PMID [39653185](https://pubmed.ncbi.nlm.nih.gov/39653185/)