# Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression.
> 脂肪肝マウスモデルにおける虚血再灌流障害に対する水素の保護効果：HO-1およびSirt1発現調節を介したメカニズムの検討


## Abstract

Fatty liver exhibits reduced tolerance to ischemia-reperfusion (I/R) injury during hepatic surgery, including transplantation. Using a methionine- and choline-deficient high-fat (MCDHF) diet-induced mouse model, this study evaluated the effects of hydrogen-rich saline (7 ppm H2) administered during I/R events. Compared with controls, the MCDHF I/R group displayed elevated serum AST and ALT, increased TUNEL-positive apoptotic cells, greater F4/80-positive macrophage infiltration, and upregulated inflammatory cytokine mRNA. Hydrogen saline administration significantly attenuated these indicators. In primary hepatocytes and Kupffer cells subjected to hypoxia/reoxygenation, hydrogen gas increased Bcl-2, HO-1, and Sirt1 expression while reducing caspase activation, Bax levels, and p53 acetylation. These findings indicate that hydrogen mitigates fatty liver I/R injury by suppressing hepatocyte apoptosis, limiting macrophage activation, and inducing cytoprotective HO-1 and Sirt1 pathways.

### Mechanism

H2 upregulates HO-1 and Sirt1 expression and increases Bcl-2 while suppressing Bax, caspase activation, and p53 acetylation, thereby reducing hepatocyte apoptosis and Kupffer cell-mediated inflammatory responses following ischemia-reperfusion in fatty liver.

## Bibliographic

- **Authors**: Li SC, Fujino M, Ichimaru N, Kurokawa R, Hirano S, Mou L, et al.
- **Journal**: Sci Rep
- **Year**: 2018 (2018-09-19)
- **PMID**: [30232347](https://pubmed.ncbi.nlm.nih.gov/30232347/)
- **DOI**: [10.1038/s41598-018-32411-4](https://doi.org/10.1038/s41598-018-32411-4)
- **PMC**: [PMC6145907](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145907/)
- **Study type**: animal study
- **Delivery route**: injection / infusion
- **Effect reported**: positive

## Delivery context

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% devices are not recommended).

## Safety notes

Intravenous hydrogen-saline infusion is a clinic-only route and is not viable for everyday self-administration. For routine hydrogen intake, inhalation is the most practical route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration 66% / 100% 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 30232347. https://h2-papers.org/en/papers/30232347
> **Source**: PubMed PMID [30232347](https://pubmed.ncbi.nlm.nih.gov/30232347/)