# Molecular Hydrogen Attenuates Chronic Inflammation and Delays the Onset of Ultraviolet B-Induced Skin Carcinogenesis in Mice.
> 分子状水素による慢性炎症の抑制と紫外線B波誘発皮膚発がんの発症遅延：マウスモデルでの検討


## Abstract

Male HR-1 hairless mice underwent chronic dorsal UVB irradiation (270 mJ/cm², three times weekly for 20 weeks) with or without continuous hydrogen exposure combining 2% H2 gas inhalation and hydrogen-rich water. Hydrogen-exposed animals showed consistently delayed papilloma onset and lower cumulative tumor counts across two independent experimental series, while squamous cell carcinoma development and survival differences reached significance in only one series. Cyclobutane pyrimidine dimer levels were unaltered, indicating no reduction in direct DNA photolesions. Hydrogen exposure reduced epidermal T-cell infiltration, dermal IL-6 concentrations, and nuclear phosphorylated STAT3, along with decreased ERK and JNK phosphorylation. The GSH/GSSG ratio was preserved after acute UVB challenge, and nuclear Nrf2 accumulation was attenuated during chronic exposure. Epidermal thickness and proliferation markers Ki-67 and PCNA were also reduced. These results indicate that continuous hydrogen administration modulates IL-6/STAT3 and ERK/JNK signaling to suppress inflammation-associated early-stage skin carcinogenesis.

### Mechanism

Hydrogen modulates IL-6/STAT3 and ERK/JNK signaling pathways, reduces epidermal T-cell infiltration and oxidative stress markers, and preserves the GSH/GSSG ratio, collectively suppressing inflammation-driven early-stage UVB-induced skin carcinogenesis without altering DNA photolesion formation.

## Bibliographic

- **Authors**: Hori F, Sobue S, Inoue C, Murakumo Y, Ichihara M
- **Journal**: Int J Mol Sci
- **Year**: 2026 (2026-01-08)
- **PMID**: [41596287](https://pubmed.ncbi.nlm.nih.gov/41596287/)
- **DOI**: [10.3390/ijms27020635](https://doi.org/10.3390/ijms27020635)
- **PMC**: [PMC12840828](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12840828/)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; 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 41596287. https://h2-papers.org/en/papers/41596287
> **Source**: PubMed PMID [41596287](https://pubmed.ncbi.nlm.nih.gov/41596287/)