# Molecular hydrogen attenuates hypoxia/reoxygenation injury of intrahepatic cholangiocytes by activating Nrf2 expression.
> Nrf2活性化を介した分子状水素による肝内胆管細胞の低酸素/再酸素化傷害に対する保護効果


## Abstract

Hypoxia/reoxygenation (H/R) injury to cholangiocytes is a recognized cause of serious biliary complications in hepatobiliary surgical procedures. Using human intrahepatic cholangiocytes, this study examined whether molecular hydrogen (H2) could reduce H/R-induced cellular damage and clarified the underlying mechanisms. H2 exposure markedly reduced cholangiocyte apoptosis following H/R. Activation of NF-E2-related factor 2 (Nrf2) and upregulation of downstream cytoprotective proteins were observed in H2-treated cells. When Nrf2 expression was silenced by RNA interference, the protective effects of H2 were abolished, indicating Nrf2 dependency. In a rat liver ischemia/reperfusion model, H2 also significantly reduced cholangiocyte apoptosis in vivo. These findings suggest that H2 shields intrahepatic cholangiocytes from H/R-induced apoptosis through a mechanism reliant on Nrf2 pathway activation.

### Mechanism

H2 activates Nrf2 transcription factor and upregulates downstream cytoprotective proteins, thereby suppressing hypoxia/reoxygenation-induced apoptosis in intrahepatic cholangiocytes; silencing Nrf2 abolishes this protective effect.

## Bibliographic

- **Authors**: Yu J, Zhang W, Zhang RJ, Jiang G, Tang H, Ruan X, et al.
- **Journal**: Toxicol Lett
- **Year**: 2015 (2015-11-04)
- **PMID**: [26276082](https://pubmed.ncbi.nlm.nih.gov/26276082/)
- **DOI**: [10.1016/j.toxlet.2015.08.010](https://doi.org/10.1016/j.toxlet.2015.08.010)
- **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 26276082. https://h2-papers.org/en/papers/26276082
> **Source**: PubMed PMID [26276082](https://pubmed.ncbi.nlm.nih.gov/26276082/)