# Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.
> 水素ガス吸入がスナネズミのウアバイン誘発性聴覚神経障害に及ぼす保護効果


## Abstract

Auditory neuropathy (AN) involves dysfunction of the auditory nerve while cochlear hair cells remain structurally intact. A Mongolian gerbil model of AN was established by applying ouabain (1 mmol/L, 20 mL) to the round window membrane. Animals were subsequently exposed to 1%, 2%, or 4% H2 gas for 60 minutes at 1 h and 6 h post-ouabain. Hearing function was assessed via auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) before and 7 days after ouabain administration. Spiral ganglion neuron (SGN) morphology and apoptosis were evaluated using TUNEL and activated caspase-3 immunofluorescence staining. Inhalation of 2% and 4% H2 significantly reduced ABR threshold shifts at 4, 8, and 16 kHz. SGN density loss and apoptotic SGN counts were markedly diminished in H2-treated animals. DPOAE amplitudes and hair cell morphology remained unaffected by either ouabain or H2 exposure. These findings indicate that H2 inhalation confers protection against ouabain-induced SGN damage primarily by suppressing apoptosis.

### Mechanism

H2 inhalation suppresses caspase-3 activation and reduces apoptotic cell death in spiral ganglion neurons, thereby limiting ouabain-induced cochlear nerve damage through anti-apoptotic mechanisms.

## Bibliographic

- **Authors**: Qu J, Gan YN, Xie K, Liu W, Wang Y, Hei RY, et al.
- **Journal**: Acta Pharmacol Sin
- **Year**: 2012
- **PMID**: [22388074](https://pubmed.ncbi.nlm.nih.gov/22388074/)
- **DOI**: [10.1038/aps.2011.190](https://doi.org/10.1038/aps.2011.190)
- **PMC**: [PMC4003360](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003360/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 1–4%

## 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 22388074. https://h2-papers.org/en/papers/22388074
> **Source**: PubMed PMID [22388074](https://pubmed.ncbi.nlm.nih.gov/22388074/)