# Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model.
> トリメチルスズ誘発神経毒性モデルマウスにおける水素ガス吸入の認知機能および酸化ストレスへの影響


## Abstract

A trimethyltin (TMT)-induced neurotoxicity model was established in C57BL/6 mice via a single intraperitoneal injection of 2.6 mg/kg TMT. Animals subsequently received 2% H2 gas inhalation for 30 minutes daily over four weeks. Spatial recognition memory assessed by Y-maze was impaired in TMT-only animals but recovered in the H2-treated group. In both serum and brain tissue, levels of ROS, nitric oxide, MDA, Apo-E, Aβ-40, phospho-tau, and Bax were reduced following H2 inhalation, while pro-inflammatory cytokines G-CSF, IL-6, and TNF-α declined significantly. Conversely, Bcl-2 and VEGF expression increased after H2 exposure. Catalase and GPx activities, which were elevated in the TMT-only group, normalized with H2 inhalation. Collectively, these findings indicate that 2% H2 gas inhalation suppresses oxidative stress, neuroinflammation, and Alzheimer's disease-related biomarkers while improving cognitive performance in a TMT mouse model, suggesting a potential role for H2 in addressing neurodegenerative conditions involving cognitive decline.

### Mechanism

H2 inhalation is proposed to reduce oxidative stress markers (ROS, MDA, NO), suppress pro-inflammatory cytokines (TNF-α, IL-6, G-CSF), downregulate pro-apoptotic Bax, and upregulate anti-apoptotic Bcl-2 and VEGF, collectively providing neuroprotection in TMT-challenged mice.

## Bibliographic

- **Authors**: Jeong ES, Bajgai J, You IS, Rahman MH, Fadriquela A, Sharma S, et al.
- **Journal**: Int J Mol Sci
- **Year**: 2021 (2021-12-10)
- **PMID**: [34948107](https://pubmed.ncbi.nlm.nih.gov/34948107/)
- **DOI**: [10.3390/ijms222413313](https://doi.org/10.3390/ijms222413313)
- **PMC**: [PMC8703468](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703468/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 2%

## 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 34948107. https://h2-papers.org/en/papers/34948107
> **Source**: PubMed PMID [34948107](https://pubmed.ncbi.nlm.nih.gov/34948107/)