# Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.
> 水素リッチウォーターによる非アルコール性脂肪肝炎の肝障害抑制：IL-10およびSirt1シグナルを介したHO-1発現増強機序の解明


## Abstract

Using a murine NASH model induced by choline-supplemented or choline-deficient amino acid-defined diets over 20 weeks, this study examined the hepatoprotective capacity of 7-ppm hydrogen-rich water (HRW) administered orally for 4, 8, or 20 weeks. HRW-treated animals showed reduced serum alanine aminotransferase and aspartate aminotransferase levels alongside attenuated histological damage. Inflammatory cytokine expression was markedly lower in HRW-receiving groups, and both hepatic steatosis and pre-established fibrosis were ameliorated. In primary hepatocytes stimulated with palmitate, molecular hydrogen activated the HO-1/AMPK/PPARα/PPARγ axis, leading to Sirt1 induction that normalized aberrant lipid metabolism. Additionally, LPS-induced cytokine production was suppressed through an HO-1/IL-10-independent mechanism. Hepatocyte apoptosis was also reversed by HRW exposure. These findings indicate that oxidative stress reduction and modulation of inflammatory signaling underlie the observed hepatoprotective effects of dissolved molecular hydrogen.

### Mechanism

Molecular hydrogen upregulates HO-1 expression, which activates the AMPK/PPARα/PPARγ pathway to induce Sirt1, thereby correcting abnormal lipid metabolism. Simultaneously, LPS-driven inflammatory cytokine production is suppressed via an HO-1/IL-10-independent route, reducing oxidative stress and hepatic inflammation.

## Bibliographic

- **Authors**: Li SC, Takahara T, Que W, Fujino M, Guo WZ, Hirano S, et al.
- **Journal**: Am J Physiol Gastrointest Liver Physiol
- **Year**: 2021 (2021-04-01)
- **PMID**: [33439102](https://pubmed.ncbi.nlm.nih.gov/33439102/)
- **DOI**: [10.1152/ajpgi.00158.2020](https://doi.org/10.1152/ajpgi.00158.2020)
- **Study type**: animal study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; 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 33439102. https://h2-papers.org/en/papers/33439102
> **Source**: PubMed PMID [33439102](https://pubmed.ncbi.nlm.nih.gov/33439102/)