# Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice.
> マウスにおける分子状水素によるSIRT1-β-カテニン経路を介した脊髄酸化ストレスおよびシナプス可塑性の抑制と慢性掻痒の軽減


## Abstract

Chronic pruritus associated with dermatitis, diabetes, and cholestasis frequently resists conventional antipruritic agents. This mouse study examined whether molecular hydrogen could suppress itch across three distinct pathological models. Both 2% H2 gas inhalation and intraperitoneal hydrogen-rich saline (5 mL/kg) reduced scratching behavior and reversed the decline in spinal SIRT1 expression and antioxidant enzyme (SOD, GPx, CAT) activity. Spinal accumulation of ROS and oxidation products (MDA, 8-OHdG, 3-NT) was diminished, alongside reductions in β-catenin acetylation and dendritic spine density. Pharmacological SIRT1 inhibition abolished these protective effects, whereas SIRT1 agonism replicated them. β-catenin inhibitors reduced ERK phosphorylation and restored antioxidant enzyme activity. Ex vivo recordings showed suppression of spontaneous excitatory postsynaptic currents, and neuroimaging revealed attenuation of cholestasis-induced functional connectivity changes between the cingulate and sensorimotor cortices. The findings indicate that SIRT1-dependent β-catenin deacetylation mediates hydrogen's antipruritic action.

### Mechanism

Molecular hydrogen upregulates spinal SIRT1, promoting β-catenin deacetylation, which in turn suppresses ROS accumulation, ERK phosphorylation, and dendritic spine remodeling, thereby reducing pruriceptive sensitization.

## Bibliographic

- **Authors**: Zhang LL, Zhao F, Song Z, Hu L, Li Y, Zhang RJ, et al.
- **Journal**: Redox Biol
- **Year**: 2025
- **PMID**: [39752998](https://pubmed.ncbi.nlm.nih.gov/39752998/)
- **DOI**: [10.1016/j.redox.2024.103472](https://doi.org/10.1016/j.redox.2024.103472)
- **PMC**: [PMC11754494](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754494/)
- **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 39752998. https://h2-papers.org/en/papers/39752998
> **Source**: PubMed PMID [39752998](https://pubmed.ncbi.nlm.nih.gov/39752998/)