# Inhalation of 4% and 67% hydrogen ameliorates oxidative stress, inflammation, apoptosis, and necroptosis in a rat model of glycerol-induced acute kidney injury.
> グリセロール誘発急性腎障害ラットモデルにおける4%および67%水素吸入による酸化ストレス・炎症・アポトーシス・ネクロプトーシスの改善


## Abstract

Using a rat model of rhabdomyolysis-associated acute kidney injury (AKI) induced by glycerol injection (8 mL/kg), this study evaluated the renoprotective effects of inhaled molecular hydrogen at two concentrations (4% and 67%) over 72 hours. Glycerol administration triggered oxidative stress, inflammatory responses, apoptosis, and necroptosis, accompanied by decreased antioxidant enzyme activity and elevated kidney injury biomarkers. H2 inhalation reversed these pathological changes and conferred renal protection. Although a consistent dose-response relationship was not observed across all AKI-related parameters, the higher concentration (67%) produced superior improvements in histological and morphological outcomes. The findings indicate that H2 inhalation may reduce rhabdomyolysis-induced renal damage through antioxidant, anti-inflammatory, anti-apoptotic, and anti-necroptotic mechanisms.

### Mechanism

H2 inhalation is proposed to preserve antioxidant enzyme activity while suppressing inflammatory signaling, apoptotic pathways, and necroptosis, collectively reducing renal cell damage in glycerol-induced AKI.

## Bibliographic

- **Authors**: Xue J, Liu B, Zhao M, Zhang MH, Wang M, Gu QQ, et al.
- **Journal**: Med Gas Res
- **Year**: 2023
- **PMID**: [36204787](https://pubmed.ncbi.nlm.nih.gov/36204787/)
- **DOI**: [10.4103/2045-9912.345169](https://doi.org/10.4103/2045-9912.345169)
- **PMC**: [PMC9555022](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555022/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 4–67%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 36204787. https://h2-papers.org/en/papers/36204787
> **Source**: PubMed PMID [36204787](https://pubmed.ncbi.nlm.nih.gov/36204787/)