# Inhalation of Hydrogen Attenuates Progression of Chronic Heart Failure via Suppression of Oxidative Stress and P53 Related to Apoptosis Pathway in Rats.
> 水素吸入による慢性心不全の進行抑制：酸化ストレスおよびp53依存性アポトーシス経路への影響（ラット実験）


## Abstract

This study examined the effects of hydrogen gas inhalation on chronic heart failure (CHF) progression using a rat model. Sixty Sprague-Dawley rats were divided into four groups—sham, sham with H2, CHF, and CHF with H2—with CHF induced by subcutaneous isoprenaline injection and confirmed via echocardiography one month later. Following H2 inhalation, cardiac function improved significantly compared with untreated CHF animals, while markers of oxidative stress damage and apoptosis were substantially reduced. In primary rat cardiomyocytes subjected to mild oxidative stress, H2 similarly decreased oxidative injury and cell death. Mechanistically, both in the rat model and in H9c2 cells, H2 markedly lowered the expression and phosphorylation of p53, a key transcription factor in the ROS–apoptosis signaling cascade. These findings indicate that molecular hydrogen can slow CHF progression by suppressing p53-regulated apoptosis.

### Mechanism

H2 reduces the expression and phosphorylation of p53, a pivotal transcription factor in the ROS–apoptosis signaling pathway, thereby decreasing cardiomyocyte apoptosis and oxidative stress-induced damage in both in vivo and in vitro settings.

## Bibliographic

- **Authors**: Chi J, Li Z, Hong X, Zhao T, Bie Y, Zhang W, et al.
- **Journal**: Front Physiol
- **Year**: 2018
- **PMID**: [30108516](https://pubmed.ncbi.nlm.nih.gov/30108516/)
- **DOI**: [10.3389/fphys.2018.01026](https://doi.org/10.3389/fphys.2018.01026)
- **PMC**: [PMC6079195](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079195/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 30108516. https://h2-papers.org/en/papers/30108516
> **Source**: PubMed PMID [30108516](https://pubmed.ncbi.nlm.nih.gov/30108516/)