# Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.
> 分子状水素による血管内皮細胞の細胞老化抑制とそのメカニズム


## Abstract

Using human umbilical vein endothelial cells (HUVECs) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a senescence model, this study investigated the effects of hydrogen-rich medium (baseline H2 concentration: 0.55±0.07 mmol/L). TCDD exposure elevated 8OHdG and acetyl-p53 levels, reduced the NAD+/NADH ratio, impaired Sirt1 activity, and increased senescence-associated β-galactosidase activity. In contrast, HUVECs cultured in hydrogen-rich medium showed none of these changes, and Nrf2 activation was concurrently observed. Notably, the protective effects persisted even after H2 became undetectable in the medium, and were abolished by chrysin, a pharmacological Nrf2 inhibitor. These findings indicate that transient H2 exposure confers durable antioxidant and anti-senescence effects in vascular endothelial cells via Nrf2 pathway activation.

### Mechanism

H2 activates the Nrf2 pathway, which suppresses TCDD-induced oxidative stress and Sirt1 activity impairment, thereby providing sustained protection against endothelial cell senescence even after H2 is no longer detectable.

## Bibliographic

- **Authors**: Hara F, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T
- **Journal**: Circ J
- **Year**: 2016 (2016-08-25)
- **PMID**: [27477846](https://pubmed.ncbi.nlm.nih.gov/27477846/)
- **DOI**: [10.1253/circj.CJ-16-0227](https://doi.org/10.1253/circj.CJ-16-0227)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. 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 not recommended).

## Safety notes

This is basic research at the cellular or molecular level. 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 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 27477846. https://h2-papers.org/en/papers/27477846
> **Source**: PubMed PMID [27477846](https://pubmed.ncbi.nlm.nih.gov/27477846/)