# Molecular hydrogen downregulates acute exhaustive exercise-induced skeletal muscle damage.
> 分子状水素の吸入が急性疲弊運動による骨格筋損傷を軽減する


## Abstract

Acute exhaustive exercise in sedentary rats causes skeletal muscle damage characterized by elevated oxidative stress, inflammatory cytokine release, and apoptotic signaling. This study examined whether inhalation of molecular hydrogen (H2) could mitigate these responses. Sedentary rats ran to exhaustion on a sealed treadmill while breathing either an H2-containing gas mixture or a control gas. Oxidative stress markers (SOD activity, GSH, TBARS), inflammatory markers (TNF-α, IL-1β, IL-6, IL-10, NF-κB phosphorylation), and apoptotic markers (cleaved caspase-3, Bcl-2, HSP70 expression) were subsequently assessed in skeletal muscle. Exercise alone did not alter SOD activity but elevated TBARS levels; H2 inhalation increased SOD activity and suppressed the TBARS rise. Exercise-induced surges in TNF-α and IL-6, along with NF-κB phosphorylation, were attenuated by H2. Additionally, the exercise-induced increase in cleaved caspase-3 expression was reduced in H2-treated animals. These findings indicate that H2 inhalation effectively suppresses multiple pathways of exercise-induced skeletal muscle damage in unaccustomed organisms.

### Mechanism

H2 inhalation enhances SOD activity to reduce lipid peroxidation (TBARS), suppresses NF-κB phosphorylation thereby lowering TNF-α and IL-6 production, and decreases cleaved caspase-3 expression, collectively attenuating exercise-induced skeletal muscle damage.

## Bibliographic

- **Authors**: Nogueira JE, Amorim MR, Pinto AP, da Rocha AL, da Silva ASR, Branco LGS
- **Journal**: Can J Physiol Pharmacol
- **Year**: 2021
- **PMID**: [33356867](https://pubmed.ncbi.nlm.nih.gov/33356867/)
- **DOI**: [10.1139/cjpp-2020-0297](https://doi.org/10.1139/cjpp-2020-0297)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## 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 33356867. https://h2-papers.org/en/papers/33356867
> **Source**: PubMed PMID [33356867](https://pubmed.ncbi.nlm.nih.gov/33356867/)