# Hydrogen promoted mitochondrial autophagy and alleviated CIH-induced vascular endothelial cell senescence by regulating oxidative stress.
> 水素による慢性間欠的低酸素誘発血管内皮細胞老化の軽減：ミトコンドリアオートファジーと酸化ストレス制御を介したメカニズム解析


## Abstract

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), accelerates vascular endothelial senescence. Using a CIH mouse model and corresponding cell model, this study examined how molecular hydrogen (H₂) affects endothelial aging. H₂ administration improved aortic pathological changes, restored vasodilatory function, reduced expression of oxidative stress and senescence markers, and elevated autophagy-related protein levels. Echocardiography, aortic ring assays, SA-β-gal staining, DHE staining, and transmission electron microscopy were employed for assessment. Mechanistic experiments showed that Nrf2 silencing diminished H₂'s capacity to attenuate endothelial senescence in the CIH cell model, indicating that H₂ activates mitochondrial autophagy and suppresses oxidative stress through an Nrf2-dependent pathway. These findings provide mechanistic evidence for the potential application of H₂ in OSA-related vascular endothelial aging.

### Mechanism

H₂ activates the Nrf2 signaling pathway, which promotes mitochondrial autophagy and reduces CIH-induced oxidative stress, thereby decreasing senescence marker expression and alleviating vascular endothelial cell aging.

## Bibliographic

- **Authors**: Li DZ, Liu Q, Fan XF, Qi K, Sun M, Song J, et al.
- **Journal**: Eur J Pharmacol
- **Year**: 2025 (2025-10-15)
- **PMID**: [40845957](https://pubmed.ncbi.nlm.nih.gov/40845957/)
- **DOI**: [10.1016/j.ejphar.2025.178078](https://doi.org/10.1016/j.ejphar.2025.178078)
- **Study type**: animal study
- **Delivery route**: animal model
- **Effect reported**: positive

## Delivery context

This study is at the animal-experiment stage. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study is at the animal-experiment stage. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; 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 40845957. https://h2-papers.org/en/papers/40845957
> **Source**: PubMed PMID [40845957](https://pubmed.ncbi.nlm.nih.gov/40845957/)