Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis.
外傷性脳損傷後の急性肺損傷に対する水素吸入の効果：パイロトーシスおよびアポトーシスへの影響
Abstract
Acute lung injury (ALI) secondary to traumatic brain injury (TBI) is a life-threatening condition in which inflammatory cascades and programmed cell death are central pathological drivers. Male Sprague-Dawley rats underwent fluid percussion injury and were subsequently exposed to 42% H2 (balanced with 21% O2 and nitrogen) for one hour daily. Animals in the TBI-only group exhibited marked pulmonary edema, elevated lung injury scores, and reduced oxygenation indices. Hydrogen inhalation significantly reduced pyroptosis-associated proteins—Caspase-1, ASC, and Gasdermin-D—alongside the pro-inflammatory cytokines IL-1β and IL-18. Apoptotic markers, including cleaved caspase-3 and the BCL-2/Bax ratio, were also favorably modulated. These findings indicate that high-concentration hydrogen inhalation accelerates endogenous recovery and attenuates both pyroptotic and apoptotic cell death pathways in TBI-induced ALI, suggesting potential utility in ICU settings.
Mechanism
Inhalation of 42% H2 suppresses pyroptosis by downregulating Caspase-1, ASC, and Gasdermin-D, while simultaneously reducing IL-1β and IL-18 levels and modulating cleaved caspase-3 and BCL-2/Bax to attenuate apoptotic cell death in lung tissue following TBI.
Bibliographic
- Authors
- Li TT, Sun T, Wang Y, Wan Q, Li W, Yang W
- Journal
- Eur J Pharmacol
- Year
- 2022 (2022-01-05)
- PMID
- 34883075
- DOI
- 10.1016/j.ejphar.2021.174664
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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