# Hydrogen molecules (H2) improve perfusion recovery via antioxidant effects in experimental peripheral arterial disease.
> 末梢動脈疾患モデルにおける水素分子の抗酸化作用を介した灌流回復促進効果


## Abstract

Peripheral arterial disease (PAD) is characterized by impaired neovascularization driven by excessive reactive oxygen species (ROS). This study examined the effects of hydrogen-saturated water in a mouse hindlimb ischemia model of PAD. Laser Doppler perfusion imaging at 14 and 21 days post-ischemia revealed that hydrogen-saturated water reduced necrosis rates and enhanced both capillary density in the gastrocnemius muscle and arterial density in the abductor muscle. Biochemical analysis of ischemic muscle at day 7 showed decreased malondialdehyde and elevated cyclic guanine monophosphate (cGMP) levels. In cultured endothelial cells, hydrogen-saturated medium lowered ROS, promoted tube formation, and raised cGMP. In macrophages, hydrogen reduced intracellular ROS and facilitated M2 polarization. These findings indicate that molecular hydrogen promotes angiogenesis and arteriogenesis, thereby improving perfusion recovery through ROS suppression.

### Mechanism

Molecular hydrogen neutralizes ROS, elevating cGMP levels in ischemic tissue. This promotes endothelial tube formation and shifts macrophage polarization toward the M2 phenotype, collectively enhancing angiogenesis and arteriogenesis in ischemic limbs.

## Bibliographic

- **Authors**: Fu J, Zou J, Chen C, Li H, Wang L, Zhou YN
- **Journal**: Mol Med Rep
- **Year**: 2018
- **PMID**: [30320393](https://pubmed.ncbi.nlm.nih.gov/30320393/)
- **DOI**: [10.3892/mmr.2018.9546](https://doi.org/10.3892/mmr.2018.9546)
- **PMC**: [PMC6236306](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236306/)
- **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 30320393. https://h2-papers.org/en/papers/30320393
> **Source**: PubMed PMID [30320393](https://pubmed.ncbi.nlm.nih.gov/30320393/)