# Mechanism of hydrogen-rich water alleviating radiation-induced cognitive impairment through PI3K/AKT/Caspase-9 pathway mediating anti-oxidation.
> PI3K/AKT/Caspase-9経路を介した抗酸化作用による水素水の放射線誘発性認知障害軽減メカニズムの解明


## Abstract

Male Sprague-Dawley rats received 20 Gy whole-brain irradiation and were subsequently administered hydrogen-rich water at high (20 mL/kg) or low (10 mL/kg) doses for 30 days. The high-dose group showed faster recovery of body weight and food intake, along with improved red blood cell and hemoglobin levels. Cognitive assessments using the Morris water maze and novel object recognition tests revealed significant improvements in the high-dose group compared with irradiation-only controls. Brain tissue analyses demonstrated reductions in ROS, MDA, and IL-6, alongside elevated SOD and GSH levels. Hippocampal neuronal apoptosis was markedly reduced in the high-dose group. At both mRNA and protein levels, PI3K and pAKT expression increased while Caspase-9 and Cytochrome c decreased. These findings indicate that hydrogen-rich water attenuates radiation-induced cognitive dysfunction through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms involving the PI3K/AKT/Caspase-9 pathway, with a discernible dose-dependent relationship.

### Mechanism

Hydrogen-rich water upregulates PI3K and AKT expression while downregulating Caspase-9 and Cytochrome c, thereby reducing radiation-induced oxidative stress and hippocampal neuronal apoptosis, ultimately preserving cognitive function.

## Bibliographic

- **Authors**: Liu M, Wang Y, Liu H, Li J, Qin X
- **Journal**: Mol Cell Biochem
- **Year**: 2025
- **PMID**: [40646375](https://pubmed.ncbi.nlm.nih.gov/40646375/)
- **DOI**: [10.1007/s11010-025-05350-8](https://doi.org/10.1007/s11010-025-05350-8)
- **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 40646375. https://h2-papers.org/en/papers/40646375
> **Source**: PubMed PMID [40646375](https://pubmed.ncbi.nlm.nih.gov/40646375/)