# Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases.
> 水素分子に対する生体応答と炎症性疾患への予防的効果


## Abstract

Molecular hydrogen (H₂) was long regarded as biologically inert in multicellular organisms due to the absence of hydrogenase. Research demonstrated that H₂ inhalation substantially reduces brain damage from focal ischemia-reperfusion by counteracting oxidative stress. Although H₂ reacts with hydroxyl radicals at a rate two to three orders of magnitude lower than conventional antioxidants, it was shown to react with Fenton reaction-derived hydroxyl radicals at room temperature without a catalyst, a property exploited in ophthalmic surgery. The anti-inflammatory actions of H₂ extend beyond reactive oxygen species scavenging; H₂ administration induces mild mitochondrial oxidative stress and activates Nrf2, a phenomenon termed mitohormesis, whereby sublethal mitochondrial stress confers cellular resilience. Crosstalk between antioxidative and anti-inflammatory signaling pathways, together with immune system modulation, is proposed as the central protective mechanism. Identifying the primary biomolecular target of H₂ is highlighted as a key objective for advancing its medical applications.

### Mechanism

H₂ scavenges Fenton reaction-derived hydroxyl radicals and simultaneously induces mild mitochondrial oxidative stress, activating Nrf2 via mitohormesis. Crosstalk between antioxidative and anti-inflammatory pathways, along with immune system regulation, underlies its cytoprotective effects.

## Bibliographic

- **Authors**: Ohsawa I
- **Journal**: Curr Pharm Des
- **Year**: 2021
- **PMID**: [32981496](https://pubmed.ncbi.nlm.nih.gov/32981496/)
- **DOI**: [10.2174/1381612826666200925123510](https://doi.org/10.2174/1381612826666200925123510)
- **Study type**: review
- **Delivery route**: mixed routes
- **Effect reported**: not assessed

## 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)

---

> **Cite as**: H2 Papers — PMID 32981496. https://h2-papers.org/en/papers/32981496
> **Source**: PubMed PMID [32981496](https://pubmed.ncbi.nlm.nih.gov/32981496/)