# Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway.
> 水素水はKeap1/Nrf2シグナル経路を介してシクロスポリンA誘発性腎毒性を軽減する


## Abstract

Chronic administration of cyclosporine A (CsA) at 25 mg/kg/day in rats produced marked oxidative stress, leading to tubular atrophy, interstitial fibrosis, tubular cell apoptosis, and vascular dysfunction, with elevated urinary protein, serum creatinine, and blood urea nitrogen indicating renal impairment. Co-administration of hydrogen-rich water (HRW) at 12 mL/kg for 4 weeks reversed these changes: reactive oxygen species and malonaldehyde levels declined, while glutathione and superoxide dismutase activity recovered. Histological analysis confirmed reduced fibrosis and apoptosis. At the molecular level, HRW suppressed Keap1 expression and upregulated Nrf2, NQO1, and HO-1, indicating activation of the antioxidant defense pathway. These findings suggest that HRW restores redox balance and protects kidney function in CsA-induced nephrotoxicity via the Keap1/Nrf2 signaling axis.

### Mechanism

HRW suppresses Keap1 expression, thereby activating Nrf2 and upregulating downstream antioxidant enzymes NQO1 and HO-1, which collectively reduce ROS and malonaldehyde while restoring glutathione and superoxide dismutase activity.

## Bibliographic

- **Authors**: Lu Y, Li CY, Ping NN, Sun YP, Wang Z, Zhao GD, et al.
- **Journal**: J Biochem Mol Toxicol
- **Year**: 2020
- **PMID**: [32040235](https://pubmed.ncbi.nlm.nih.gov/32040235/)
- **DOI**: [10.1002/jbt.22467](https://doi.org/10.1002/jbt.22467)
- **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 32040235. https://h2-papers.org/en/papers/32040235
> **Source**: PubMed PMID [32040235](https://pubmed.ncbi.nlm.nih.gov/32040235/)