# Oxidative Stress and Pathways of Molecular Hydrogen Effects in Medicine.
> 医学における分子状水素の酸化ストレスへの影響と作用経路に関する総説


## Abstract

Excessive reactive oxygen species (ROS) generated during radiation exposure, ischemia-reperfusion events, and inflammatory states damage proteins, lipids, and nucleic acids while disrupting cell signaling. Although exogenous antioxidant supplementation has been proposed as a countermeasure, clinical outcomes have generally been unfavorable. Molecular hydrogen (H₂) offers a distinct mechanistic profile: it selectively neutralizes hydroxyl radicals without eliminating ROS species required for normal cellular signaling. Beyond direct radical scavenging, H₂ modulates multiple biological processes — including inflammation, apoptosis, and autophagy — through indirect regulation of signal transduction and gene expression. Activation of the Keap1-Nrf2-ARE pathway by H₂ contributes to redox homeostasis and adaptive stress responses. Crosstalk among MAPKs, p53, NF-κB, p38 MAPK, and mTOR further accounts for the broad, pleiotropic actions observed across diverse pathological conditions. This review synthesizes current understanding of these interconnected pathways to explain the wide-ranging biological effects attributed to H₂.

### Mechanism

H₂ selectively scavenges hydroxyl radicals and activates the Keap1-Nrf2-ARE pathway to restore redox balance. It also modulates apoptosis and autophagy through crosstalk involving MAPKs, p53, NF-κB, p38 MAPK, and mTOR signaling networks.

## Bibliographic

- **Authors**: Slezak J, Kura B, LeBaron TW, Singal PK, Buday J, Barancik M
- **Journal**: Curr Pharm Des
- **Year**: 2021
- **PMID**: [32954996](https://pubmed.ncbi.nlm.nih.gov/32954996/)
- **DOI**: [10.2174/1381612826666200821114016](https://doi.org/10.2174/1381612826666200821114016)
- **Study type**: review
- **Delivery route**: not specified
- **Effect reported**: not assessed

## Delivery context

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices 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)

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> **Cite as**: H2 Papers — PMID 32954996. https://h2-papers.org/en/papers/32954996
> **Source**: PubMed PMID [32954996](https://pubmed.ncbi.nlm.nih.gov/32954996/)