# Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment.
> 水素分子がメタンフェタミン誘発神経毒性および空間記憶障害に及ぼす影響


## Abstract

Methamphetamine (METH) is a highly addictive stimulant whose high-dose exposure causes irreversible hippocampal neuronal damage and cognitive dysfunction. Male C57BL/6 mice received four intraperitoneal injections of METH (10 mg/kg at 3-hour intervals), followed by 7 days of hydrogen-rich water (HRW) consumption. Spatial learning and memory were assessed using the Barnes maze and Morris water maze. HRW intake significantly suppressed METH-induced spatial memory deficits and hippocampal neuronal injury. At the molecular level, HRW reduced elevated Bax/Bcl-2 ratios, cleaved caspase-3, GRP78, CHOP, and p-NF-κB p65 expression, as well as hippocampal IL-6 and TNF-α concentrations. These findings suggest that molecular hydrogen delivered via HRW may reduce the risk of neurodegeneration associated with METH exposure.

### Mechanism

HRW consumption suppressed METH-induced hippocampal neurodegeneration by reducing apoptosis via the Bax/Bcl-2/caspase-3 pathway, attenuating endoplasmic reticulum stress markers (GRP78, CHOP), and inhibiting NF-κB-mediated neuroinflammation (IL-6, TNF-α).

## Bibliographic

- **Authors**: Wen D, Hui R, Wang J, Shen XL, Xie B, Gong M, et al.
- **Journal**: Front Pharmacol
- **Year**: 2019
- **PMID**: [31396089](https://pubmed.ncbi.nlm.nih.gov/31396089/)
- **DOI**: [10.3389/fphar.2019.00823](https://doi.org/10.3389/fphar.2019.00823)
- **PMC**: [PMC6664236](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664236/)
- **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 31396089. https://h2-papers.org/en/papers/31396089
> **Source**: PubMed PMID [31396089](https://pubmed.ncbi.nlm.nih.gov/31396089/)