# Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH).
> 非アルコール性脂肪肝炎（NASH）の病態における酸化ストレスを含む多重ヒット機序と分子状水素の役割


## Abstract

NASH progression involves multiple concurrent factors—genetic variation, insulin resistance, and gut microbiota—that converge at the cellular level to drive adipokine secretion, endoplasmic reticulum stress, and oxidative stress, ultimately producing hepatic steatosis, inflammation, and fibrosis. Among these, oxidative stress is regarded as a pivotal driver of the transition from simple fatty liver to NASH. Short-term clinical trials of antioxidant approaches have demonstrated control of hepatitis activity, yet long-term outcomes remain unclear; trials targeting cerebrovascular disease and cancer using non-selective antioxidants have largely been unsuccessful. Molecular hydrogen offers a more selective alternative, scavenging only cytotoxic reactive oxygen species without disturbing physiological redox signaling. Evidence suggests that hydrogen-rich water can suppress the progression from NASH to hepatocellular carcinoma, pointing to mitochondrial oxidative stress as a promising intervention target. Extended clinical studies are required to address this multifactorial, lifestyle-related condition.

### Mechanism

Molecular hydrogen selectively neutralizes cytotoxic reactive oxygen species without affecting beneficial redox signals, thereby reducing mitochondrial oxidative stress implicated in NASH progression to hepatocellular carcinoma.

## Bibliographic

- **Authors**: Takaki A, Kawai D, Yamamoto K
- **Journal**: Int J Mol Sci
- **Year**: 2013 (2013-10-15)
- **PMID**: [24132155](https://pubmed.ncbi.nlm.nih.gov/24132155/)
- **DOI**: [10.3390/ijms141020704](https://doi.org/10.3390/ijms141020704)
- **PMC**: [PMC3821639](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821639/)
- **Study type**: review
- **Delivery route**: hydrogen-rich water
- **Effect reported**: not assessed

## 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 24132155. https://h2-papers.org/en/papers/24132155
> **Source**: PubMed PMID [24132155](https://pubmed.ncbi.nlm.nih.gov/24132155/)