# Effects of Hydrogen-rich Water on the PI3K/AKT Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury.
> 水素水がラット心筋虚血再灌流傷害におけるPI3K/AKTシグナル経路に及ぼす影響


## Abstract

Using a Langendorff isolated heart preparation, 60 rats were allocated to hydrogen-rich water or control groups, each subdivided into pre-ischemic, ischemic, and reperfusion subgroups (n=10 per subgroup). Control hearts received Krebs-Ringer solution alone, while the hydrogen-rich water group received Krebs-Ringer solution supplemented with hydrogen-rich water. Gene and protein expression of PI3K, AKT, phosphorylated AKT, FoxO1, Bim, and Caspase-3 were quantified by RT-qPCR, immunohistochemistry, and Western blotting, with Caspase-3 enzymatic activity assessed spectrophotometrically. In the hydrogen-rich water reperfusion subgroup, PI3K, AKT, and p-AKT expression were elevated, whereas FoxO1, Bim, and Caspase-3 levels were significantly reduced relative to the corresponding control subgroup (P<0.05). These findings indicate that hydrogen-rich water activates the PI3K/AKT signaling cascade, thereby suppressing cardiomyocyte apoptosis and reducing myocardial ischemia-reperfusion injury in isolated rat hearts.

### Mechanism

Hydrogen-rich water activates the PI3K/AKT signaling pathway, leading to downregulation of FoxO1, Bim, and Caspase-3 expression, which collectively reduces cardiomyocyte apoptosis during ischemia-reperfusion.

## Bibliographic

- **Authors**: Li L, Li XM, Zhang Z, Liu L, Liu TT, Li SC, et al.
- **Journal**: Curr Mol Med
- **Year**: 2020
- **PMID**: [31702499](https://pubmed.ncbi.nlm.nih.gov/31702499/)
- **DOI**: [10.2174/1566524019666191105150709](https://doi.org/10.2174/1566524019666191105150709)
- **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 31702499. https://h2-papers.org/en/papers/31702499
> **Source**: PubMed PMID [31702499](https://pubmed.ncbi.nlm.nih.gov/31702499/)