# Inhalation of H/O(66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage.
> H₂/O₂（66.7%/33.3%）吸入による糖尿病合併うつ病マウスの抑うつ様行動抑制：炎症抑制と海馬保護を介したメカニズム


## Abstract

Diabetes mellitus complicated with depression (DD) is a psychosomatic condition associated with cognitive impairment and elevated disability risk. Using a mouse model induced by intraperitoneal streptozotocin (150 mg/kg) and lipopolysaccharide (0.5 mg/kg), this study examined the effects of H2/O2 (66.7%/33.3%) inhalation administered for 7 consecutive days. Standard behavioral tests revealed marked reduction in depressive-like behaviors. ELISA measurements showed decreased inflammatory cytokine concentrations in both peripheral serum and hippocampal tissue. MRI and immunofluorescence analyses demonstrated recovery of hippocampal volume and suppression of A1 astrocyte activation. These findings indicate that H2/O2 inhalation exerts beneficial effects on DD-related behavioral and neuroinflammatory endpoints in this preclinical model.

### Mechanism

H2 acts as a selective hydroxyl radical scavenger, reducing inflammatory cytokine levels in serum and hippocampal tissue while suppressing A1 astrocyte activation, thereby preserving hippocampal structural integrity in DD mice.

## Bibliographic

- **Authors**: Fan H, Shi Y, Liu H, Zuo X, Yang Y, Yin H, et al.
- **Journal**: Biomed Pharmacother
- **Year**: 2024
- **PMID**: [39405908](https://pubmed.ncbi.nlm.nih.gov/39405908/)
- **DOI**: [10.1016/j.biopha.2024.117559](https://doi.org/10.1016/j.biopha.2024.117559)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 66.7%

## 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 39405908. https://h2-papers.org/en/papers/39405908
> **Source**: PubMed PMID [39405908](https://pubmed.ncbi.nlm.nih.gov/39405908/)