# Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway.
> Nrf2/HO-1シグナル経路を介した水素分子による敗血症マウスの血管内皮障害抑制効果


## Abstract

This study examined the protective role of molecular hydrogen (H2) against endothelial injury in sepsis using LPS-stimulated human umbilical vein endothelial cells (HUVECs) and a cecal ligation and puncture (CLP) mouse model. H2-rich medium at 0.3 and 0.6 mmol/L improved cell viability and reduced apoptosis in LPS-challenged HUVECs, with the saturated concentration showing optimal efficacy. H2 suppressed adhesion molecules VCAM-1 and ICAM-1, as well as pro-inflammatory mediators TNF-α, IL-1β, and HMGB1, while elevating anti-inflammatory IL-10 in both cell and lung tissue preparations. HO-1 expression and enzymatic activity were enhanced by H2 in vitro and in vivo; pharmacological inhibition of HO-1 reversed these effects. Studies in Nrf2-knockout mice confirmed that the endothelial protective actions of H2 depend on intact Nrf2/HO-1 signaling, indicating that this pathway mediates H2-associated suppression of excessive inflammatory responses during sepsis.

### Mechanism

H2 activates Nrf2, upregulating HO-1 expression and activity, which in turn suppresses adhesion molecules (VCAM-1, ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1β, HMGB1) while elevating IL-10, thereby reducing endothelial injury and systemic inflammation in sepsis.

## Bibliographic

- **Authors**: Chen H, Xie K, Han H, Li Y, Liu L, Yang T, et al.
- **Journal**: Int Immunopharmacol
- **Year**: 2015
- **PMID**: [26253656](https://pubmed.ncbi.nlm.nih.gov/26253656/)
- **DOI**: [10.1016/j.intimp.2015.07.034](https://doi.org/10.1016/j.intimp.2015.07.034)
- **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 26253656. https://h2-papers.org/en/papers/26253656
> **Source**: PubMed PMID [26253656](https://pubmed.ncbi.nlm.nih.gov/26253656/)