# Long-Term Consumption of Hydrogen-Rich Water Mitigates Oxidative Stress, Hepatic Inflammation, and Apoptosis in Rats with LPS-Induced Chronic Liver Injury.
> 水素水の長期摂取がLPS誘発慢性肝障害ラットにおける酸化ストレス・肝炎症・アポトーシスを軽減する


## Abstract

Chronic hepatic inflammation underlies the progression of various metabolic liver diseases, yet the long-term effects of hydrogen-rich water (HRW) on this condition had not been well characterized. Sprague-Dawley rats received HRW for 8 months before and during exposure to lipopolysaccharide (LPS) to establish a chronic liver injury model. Sustained HRW administration suppressed inflammatory cell infiltration in hepatic tissue, blunted abnormal rises in pro-inflammatory mediators, and stabilized anti-inflammatory factor expression. Apoptotic signaling through the death receptor, mitochondrial, and endoplasmic reticulum stress pathways—reflected by Bax, cytochrome c, Caspase-3, -8, -9, -12, CHOP, and GRP78—was attenuated, while the anti-apoptotic protein Bcl-2 was preserved. These findings indicate that long-term HRW consumption may delay chronic inflammation-driven liver injury by concurrently reducing oxidative stress, mitochondrial dysfunction, and apoptotic activity.

### Mechanism

HRW suppresses pro-apoptotic signaling via the death receptor, mitochondrial, and ER stress pathways—downregulating Bax, Caspase-3/-8/-9/-12, CHOP, and GRP78—while maintaining Bcl-2 expression, thereby reducing hepatocyte apoptosis and oxidative stress-driven liver injury.

## Bibliographic

- **Authors**: Zhang LL, Wang H, Mai Y, He Q, Liu TT, Zhang N, et al.
- **Journal**: Antioxidants (Basel)
- **Year**: 2026 (2026-02-18)
- **PMID**: [41750640](https://pubmed.ncbi.nlm.nih.gov/41750640/)
- **DOI**: [10.3390/antiox15020260](https://doi.org/10.3390/antiox15020260)
- **PMC**: [PMC12938009](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12938009/)
- **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 41750640. https://h2-papers.org/en/papers/41750640
> **Source**: PubMed PMID [41750640](https://pubmed.ncbi.nlm.nih.gov/41750640/)