Molecular hydrogen protects against sepsis-induced cardiomyopathy through improving Golgi stress-mediated autophagy, inflammation and apoptosis.
分子状水素は敗血症誘発性心筋症においてゴルジストレス介在性のオートファジー・炎症・アポトーシスを調節することで心保護効果を発揮する
Abstract
Sepsis-induced cardiomyopathy (SIC) represents a leading contributor to sepsis mortality. Using a caecal ligation and puncture (CLP) mouse model, this study examined the effects of 2% H2 inhalation on cardiac outcomes. CLP reduced 7-day survival, impaired cardiac function, elevated myocardial damage enzymes, and was accompanied by Golgi apparatus (GA) structural changes alongside heightened autophagy, inflammation, and apoptosis. Inhalation of 2% H2 reversed these deteriorations. Critically, co-administration of the GA stress-specific agonist Brefeldin A abolished the beneficial effects of H2, confirming that Golgi stress is a key mediator. Immunofluorescence and electron microscopy corroborated GA morphological alterations. These findings indicate that H2 confers cardiac protection in SIC by suppressing Golgi stress and its downstream cascades governing autophagy, inflammatory signaling, and cell death pathways.
Mechanism
H2 inhalation suppresses Golgi apparatus stress in septic cardiomyocytes, thereby reducing downstream activation of autophagy, pro-inflammatory signaling, and apoptotic pathways, collectively attenuating myocardial injury in CLP-induced sepsis.
Bibliographic
- Authors
- Meng S, Liu J, Luo YX, Fan Y, Wang Z, Song Y, et al.
- Journal
- Br J Pharmacol
- Year
- 2025
- PMID
- 40717465
- DOI
- 10.1111/bph.70132
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
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