# Effect of hydrogen-rich water on the Nrf2/ARE 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Nrf2/AREシグナル経路に及ぼす影響


## Abstract

Using a Langendorff-perfused isolated heart preparation, 60 rats were allocated equally to a hydrogen-rich water group or a control group, each further subdivided into pre-ischemic, ischemic, and reperfusion phases. The control hearts received Krebs-Ringer solution alone, while the experimental group received Krebs-Ringer supplemented with hydrogen-rich water. RT-qPCR, immunohistochemistry, and Western blot analyses revealed that mRNA and protein levels of Nrf2, NQO1, HO-1, and SOD-1 were significantly elevated during the reperfusion phase in the hydrogen-rich water group compared with the ischemic phase (P < 0.05), whereas the same markers declined significantly in controls. Correspondingly, SOD enzymatic activity rose and malondialdehyde content fell in the hydrogen-rich water group during reperfusion, with the opposite pattern observed in controls. These findings indicate that hydrogen-rich water activates the Nrf2/ARE signaling cascade, thereby reducing oxidative stress in myocardial tissue subjected to ischemia-reperfusion.

### Mechanism

Hydrogen-rich water activates the Nrf2/ARE pathway, upregulating downstream antioxidant genes NQO1, HO-1, and SOD-1, which enhances SOD enzymatic activity and suppresses malondialdehyde accumulation, collectively reducing oxidative stress in ischemia-reperfusion-injured myocardium.

## Bibliographic

- **Authors**: Li L, Liu TT, Liu L, Li SC, Zhang Z, Zhang RJ, et al.
- **Journal**: J Bioenerg Biomembr
- **Year**: 2019
- **PMID**: [31768722](https://pubmed.ncbi.nlm.nih.gov/31768722/)
- **DOI**: [10.1007/s10863-019-09814-7](https://doi.org/10.1007/s10863-019-09814-7)
- **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)

---

> **Cite as**: H2 Papers — PMID 31768722. https://h2-papers.org/en/papers/31768722
> **Source**: PubMed PMID [31768722](https://pubmed.ncbi.nlm.nih.gov/31768722/)