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Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival.

高齢マウスのLPS誘発炎症モデルにおける2%水素ガス持続吸入による肺障害軽減効果

animal study inhalation mixed 1–2%

Abstract

Against the backdrop of rising sepsis incidence in aging populations, this animal study examined the effects of hydrogen gas inhalation on LPS-induced systemic inflammation in 21–23-month-old male mice. Eight experimental groups were established, varying H2 concentration (1% or 2%) and exposure duration (1, 6, or 24 hours). Only the 24-hour 2% H2 inhalation regimen produced significant improvements: survival rates and locomotor activity increased, while mRNA levels of inflammatory markers in lung and liver tissue declined. Lung-specific senescence-associated molecules—including CXCL2, MMP-3, arginase-1, and the cell-cycle inhibitor p21—were also downregulated. Hepatic injury induced by LPS was not meaningfully altered under any tested condition. These findings indicate that prolonged, higher-concentration H2 inhalation selectively modulates pulmonary inflammation and aging-related molecular signatures in elderly mice.

Mechanism

Continuous inhalation of 2% H2 for 24 hours suppressed mRNA expression of inflammatory cytokines and senescence-associated proteins (CXCL2, MMP-3, arginase-1, p21) in lung tissue, thereby reducing LPS-induced pulmonary injury in aged mice.

Bibliographic

Authors
Aokage T, Iketani M, Seya M, Meng Y, Ageta K, Naito H, et al.
Journal
Exp Gerontol
Year
2023
PMID
37572992
DOI
10.1016/j.exger.2023.112270

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.

→ Evidence by delivery route

Safety notes

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.

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