# Molecular hydrogen mitigates acetaminophen-induced liver injury and enhances the effects of N-acetylcysteine in diabetic mice.
> 糖尿病マウスにおける分子状水素のアセトアミノフェン誘発性肝障害軽減効果およびN-アセチルシステインとの相乗作用


## Abstract

Diabetic db/db mice were given hydrogen-dissolved water for two weeks before acetaminophen (APAP) overdose. Hydrogen water consumption led to marked reductions in plasma ALT and AST levels alongside improved liver histology. Using redox-sensitive GFP transgenic mice, both cytosolic and mitochondrial oxidative stress were found to be substantially diminished. Mechanistically, hydrogen modulated JNK activation, blocked mitochondrial Bax translocation, and suppressed mitochondrial endonuclease release. Expression of the hepatoprotective factor FGF21 was also upregulated. Compared with N-acetylcysteine (NAC) alone, co-administration of hydrogen and NAC conferred greater hepatoprotection, an effect attributed to complementary influences on mitochondrial oxidative stress and FGF21 regulation. These results indicate that hydrogen water may offer additive benefit alongside NAC in APAP-induced liver injury under diabetic conditions.

### Mechanism

Hydrogen suppresses JNK activation, inhibits mitochondrial Bax translocation and endonuclease release, and upregulates FGF21 expression, collectively reducing APAP-induced mitochondrial and cytosolic oxidative stress in diabetic liver.

## Bibliographic

- **Authors**: Kamimura N, Iuchi K, Igarashi T, Ohsawa I, Nito C, Usuda J, et al.
- **Journal**: J Nutr Biochem
- **Year**: 2026
- **PMID**: [41207540](https://pubmed.ncbi.nlm.nih.gov/41207540/)
- **DOI**: [10.1016/j.jnutbio.2025.110176](https://doi.org/10.1016/j.jnutbio.2025.110176)
- **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 41207540. https://h2-papers.org/en/papers/41207540
> **Source**: PubMed PMID [41207540](https://pubmed.ncbi.nlm.nih.gov/41207540/)