# Molecular hydrogen as a novel regulator of cellular pyroptosis: mechanistic insights and therapeutic implications.
> 細胞ピロトーシスの新規調節因子としての分子状水素：作用機序と疾患への応用に関するレビュー


## Abstract

Pyroptosis is an inflammatory form of programmed cell death characterized by gasdermin-mediated membrane pore formation and extensive cytokine release, contributing to the pathogenesis of multiple diseases. This review presents a mechanistic framework in which molecular hydrogen modulates pyroptosis via three interconnected axes: direct redox modification of gasdermin proteins, integration of mitochondrial signaling, and disruption of inflammasome assembly. Analysis across disease models including cardiac ischemia-reperfusion injury, neuroinflammation, metabolic disorders, and cancer reveals context-dependent effects of hydrogen — cytoprotective in normal tissues yet capable of promoting pyroptosis in malignant cells. Temporally, hydrogen's actions shift from rapid antioxidant responses to sustained anti-inflammatory effects, with notable tissue specificity. Although preclinical data support efficacy in myocardial injury, neurodegeneration, and systemic inflammation, translational challenges such as delivery optimization, dosimetric standardization, and biomarker identification remain unresolved. The review outlines a research roadmap to bridge these gaps.

### Mechanism

Hydrogen regulates pyroptosis by directly modifying gasdermin proteins through redox reactions, modulating mitochondrial signaling cascades, and inhibiting inflammasome assembly. These mechanisms exhibit tissue specificity, conferring cytoprotection in normal cells while facilitating pyroptotic cell death in malignant cells.

## Bibliographic

- **Authors**: Ye Y, Yu Z, Nie L, Lu B, Mu G
- **Journal**: Mol Biol Rep
- **Year**: 2025 (2025-06-26)
- **PMID**: [40569354](https://pubmed.ncbi.nlm.nih.gov/40569354/)
- **DOI**: [10.1007/s11033-025-10757-z](https://doi.org/10.1007/s11033-025-10757-z)
- **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 40569354. https://h2-papers.org/en/papers/40569354
> **Source**: PubMed PMID [40569354](https://pubmed.ncbi.nlm.nih.gov/40569354/)