# Hydrogen-Rich Water Ameliorates Murine Chronic Graft-versus-Host Disease through Antioxidation.
> 水素水の経口投与による慢性移植片対宿主病マウスモデルへの抗酸化的改善効果


## Abstract

Chronic graft-versus-host disease (cGVHD) is a major life-threatening complication following allogeneic hematopoietic stem cell transplantation, and available interventions remain insufficient. Using a haploidentical bone marrow transplantation mouse model of scleroderma-type cGVHD, this study examined the effects of orally administered hydrogen-rich water. The one-month survival rate in the hydrogen group reached 93.3%, significantly exceeding the 66.7% observed in controls. At 96 days post-transplantation, clinical scores (2.2 vs. 4.5) and skin histopathological scores by both H&E and Masson staining were markedly lower in hydrogen-treated animals. Skin tissue expression of antioxidant enzymes HO-1 and NQO1 was elevated in cGVHD mice but was substantially reduced in the hydrogen group. Additionally, caspase-3 protein levels, a marker of apoptosis, were lower in hydrogen-treated mice (4.36 vs. 7.17). These findings indicate that hydrogen-rich water alleviates cGVHD pathology through antioxidant and anti-apoptotic mechanisms, supporting further clinical investigation.

### Mechanism

Hydrogen-rich water suppresses excessive upregulation of antioxidant enzymes HO-1 and NQO1 in skin tissue, reflecting reduced oxidative stress, while also decreasing caspase-3 expression, thereby attenuating apoptosis-driven pathology in cGVHD.

## Bibliographic

- **Authors**: Qian L, Liu J, Ma W, Liu Y, Wang X, Liu DQ
- **Journal**: Oxid Med Cell Longev
- **Year**: 2021
- **PMID**: [34691352](https://pubmed.ncbi.nlm.nih.gov/34691352/)
- **DOI**: [10.1155/2021/1165928](https://doi.org/10.1155/2021/1165928)
- **PMC**: [PMC8531770](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531770/)
- **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 34691352. https://h2-papers.org/en/papers/34691352
> **Source**: PubMed PMID [34691352](https://pubmed.ncbi.nlm.nih.gov/34691352/)