# Long-term consumption of hydrogen-rich water provides hepatoprotection by improving mitochondrial biology and quality control in chronically stressed mice.
> 慢性ストレスマウスにおける水素水長期摂取によるミトコンドリア機能改善を介した肝保護効果


## Abstract

Chronic stress poses substantial risks to hepatic function in modern populations. This animal study examined the effects of 7-month hydrogen-rich water (HRW) administration in mice subjected to the chronic unpredictable mild stress (CUMS) protocol. Histological assessment revealed improved liver morphology in HRW-treated animals, accompanied by normalization of AST and ALT levels. Antioxidant enzyme activities (SOD, CAT, GSH) were elevated, and mitochondrial reactive oxygen species were reduced. Mitochondrial biogenesis markers—Nrf1, PGC-1α, and Tfam—were upregulated, with corresponding increases in ATP output. Ferroptosis-related indicators (MDA, 4-HNE, Fe) declined, and GPX4 and SLC7A11 expression rose via the Nrf2/HO-1 pathway. Apoptotic signaling was attenuated, as shown by decreased Bax, Cytochrome c, Caspase-3, and Caspase-8 alongside increased Bcl-2. Mitochondrial quality-control proteins governing fission, fusion, and mitophagy were also modulated. Collectively, these findings indicate that HRW exerts multi-mechanistic hepatoprotection under chronic stress conditions.

### Mechanism

HRW scavenges mitochondrial ROS and activates antioxidant enzymes (SOD, CAT, GSH), promoting mitochondrial biogenesis via Nrf1/PGC-1α/Tfam. Ferroptosis is suppressed through the Nrf2/HO-1 pathway with upregulation of GPX4 and SLC7A11, while apoptosis is attenuated by shifting Bcl-2/Bax balance and reducing caspase activation.

## Bibliographic

- **Authors**: He Q, Lan X, Ding MY, Zhang N
- **Journal**: PLoS One
- **Year**: 2025
- **PMID**: [39951412](https://pubmed.ncbi.nlm.nih.gov/39951412/)
- **DOI**: [10.1371/journal.pone.0317080](https://doi.org/10.1371/journal.pone.0317080)
- **PMC**: [PMC11828380](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828380/)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 39951412. https://h2-papers.org/en/papers/39951412
> **Source**: PubMed PMID [39951412](https://pubmed.ncbi.nlm.nih.gov/39951412/)