# Oral Hydrogen-Rich Water Alleviates Oxalate-Induced Kidney Injury by Suppressing Oxidative Stress, Inflammation, and Fibrosis.
> 水素水経口投与によるシュウ酸誘発性腎障害の軽減：酸化ストレス・炎症・線維化への影響


## Abstract

Using a mouse model of calcium oxalate (CaOx) crystallization induced by a high-oxalate diet, this study examined the renal protective effects of hydrogen-rich water (HRW). Oxalate feeding elevated crystal deposition, tubular damage, fibrosis, and reactive oxygen species (ROS) in kidney tissue, along with serum markers of renal injury, inflammation, and oxidative stress. HRW administration reduced all these parameters. RNA sequencing identified 3,566 differentially expressed genes, with pathway enrichment analysis highlighting PI3K/AKT, NF-κB, and TGF-β signaling. Western blotting and immunohistochemistry confirmed that oxalate-induced upregulation of key molecules in these pathways—including PI3K, AKT, p-AKT, NF-κB p65, NLRP3, IL-1β, TGF-β, TGF-βRI, TGF-βRII, p-Smad2, and p-Smad3—was attenuated by HRW. The findings suggest that HRW exerts antioxidant, anti-inflammatory, and antifibrotic effects in oxalate-induced kidney injury through coordinated inhibition of these three pathways.

### Mechanism

HRW downregulates PI3K/AKT, NF-κB, and TGF-β signaling pathways, thereby reducing oxalate-driven oxidative stress, inflammatory cytokine production (including NLRP3 and IL-1β), and fibrotic mediator expression (Smad2/3) in renal tissue.

## Bibliographic

- **Authors**: Si Y, Liu L, Cheng J, Zhao T, Zhou Q, Yu J, et al.
- **Journal**: Front Med (Lausanne)
- **Year**: 2021
- **PMID**: [34490303](https://pubmed.ncbi.nlm.nih.gov/34490303/)
- **DOI**: [10.3389/fmed.2021.713536](https://doi.org/10.3389/fmed.2021.713536)
- **PMC**: [PMC8418222](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418222/)
- **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 34490303. https://h2-papers.org/en/papers/34490303
> **Source**: PubMed PMID [34490303](https://pubmed.ncbi.nlm.nih.gov/34490303/)