# Effect of Htreatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease.
> 関節リウマチ関連間質性肺疾患マウスモデルにおける水素の効果


## Abstract

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is a leading cause of death in RA patients, yet available interventions remain scarce. Using D1CC transgenic mice that aberrantly express MHC class II genes and develop collagen II-induced polyarthritis resembling human RA, this study examined the progression of chronic lung fibrosis and the influence of hydrogen-rich water. Mice received type II collagen injections and were supplied either hydrogen-rich or control water for 10 months. At endpoint, elevated serum surfactant protein D and increased lung density were observed. Lung tissue showed higher numbers of 8-hydroxy-2'-deoxyguanosine-positive cells alongside elevated TNF-α, BAX, TGF-β, IL-6, and soluble collagen levels, with patchy inflammation concentrated in perilymphatic stromal regions. Hydrogen-rich water administration reduced all these pathological markers. The findings indicate that oxidative stress attenuation by molecular hydrogen may underlie its protective role against RA-ILD progression in this model.

### Mechanism

Molecular hydrogen permeates cell membranes and scavenges reactive oxygen species, thereby reducing 8-OHdG formation and suppressing TNF-α, TGF-β, IL-6, and BAX upregulation, which collectively attenuates pulmonary inflammation and fibrosis in RA-associated ILD.

## Bibliographic

- **Authors**: Terasaki Y, Terasaki M, Kanazawa S, Kokuho N, Urushiyama H, Kajimoto Y, et al.
- **Journal**: J Cell Mol Med
- **Year**: 2019
- **PMID**: [31424157](https://pubmed.ncbi.nlm.nih.gov/31424157/)
- **DOI**: [10.1111/jcmm.14603](https://doi.org/10.1111/jcmm.14603)
- **PMC**: [PMC6787460](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787460/)
- **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 31424157. https://h2-papers.org/en/papers/31424157
> **Source**: PubMed PMID [31424157](https://pubmed.ncbi.nlm.nih.gov/31424157/)