H₂ Papers

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Hydrogen ameliorates lung injury in a rat model of subacute exposure to concentrated ambient PM2.5 via Aryl hydrocarbon receptor.

大気中PM2.5への亜急性曝露ラットモデルにおける水素の肺傷害軽減効果とアリール炭化水素受容体を介したメカニズムの検討

animal study inhalation positive 66.7%

Abstract

Using a rat model of subacute concentrated ambient PM2.5 exposure (1328 ± 730 µg/m³, 5 h/day, 5 days/week for 4 weeks), this study examined whether 66.7% hydrogen inhalation (2 h/day post-exposure) could protect against pulmonary damage. PM2.5-exposed animals showed deteriorated lung function, histopathological changes, airway mucus hypersecretion (elevated MUC5AC expression by immunohistochemistry and RT-qPCR), increased pro-inflammatory cytokines (TNF-α, IL-8, IL-1β), and elevated oxidative stress markers (MDA and 8-isoprostane F2α). Hydrogen inhalation significantly attenuated all these parameters. Western blot analysis revealed that PM2.5 exposure reduced aryl hydrocarbon receptor (AhR) protein levels in lung tissue, and hydrogen inhibited this AhR downregulation. These findings suggest that hydrogen exerts its pulmonary protective effects at least partly through AhR-dependent signaling.

Mechanism

H2 inhalation prevents PM2.5-induced downregulation of aryl hydrocarbon receptor (AhR) in lung tissue, thereby suppressing downstream oxidative stress and pro-inflammatory cytokine production, which collectively reduces pulmonary injury.

Bibliographic

Authors
Feng S, Duan E, Shi X, Zhang H, Li H, Zhao Y, et al.
Journal
Int Immunopharmacol
Year
2019
PMID
31718930
DOI
10.1016/j.intimp.2019.105939

Tags

Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) immune modulation (180) anti-inflammatory (743) lipid peroxidation (238) oxidative stress (899) reactive oxygen species (774)

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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