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Evaluation of the therapeutic effects of nebulized inhalation of hydrogen-rich water on primary blast lung injury in C57BL/6 mice.

水素富化水ネブライザー吸入による一次爆風肺損傷に対する効果：C57BL/6マウスを用いた検討

animal study inhalation positive

Abstract

This animal study investigated the effects of nebulized hydrogen-rich water on primary blast lung injury in C57BL/6 mice. A total of 150 mice (aged 6–8 weeks) were randomly assigned to a hydrogen-rich water nebulization group or a control group (n=75 each) and subjected to blast overpressure of 266±9.156 kPa. Assessments at 6, 12, 24, and 48 hours post-injury showed that the hydrogen-rich water group had significantly higher survival rates (81.3% vs 61.3% at 24 hours, P<0.01). Pulmonary function improved, with greater tidal volume, normalized respiratory rate, and higher minute ventilation. Arterial blood gas analysis demonstrated enhanced oxygenation and reduced hypercapnia. Histological findings indicated less pulmonary edema and hemorrhage. Inflammatory cytokines (IL-1β, IL-6, TNF-α) and the oxidative stress marker malondialdehyde were significantly reduced, while total superoxide dismutase activity was elevated in the hydrogen-rich water group compared with controls (P<0.01).

Mechanism

Hydrogen's antioxidant properties suppress malondialdehyde production and enhance superoxide dismutase activity, while its anti-inflammatory action reduces IL-1β, IL-6, and TNF-α levels, collectively limiting alveolar and capillary damage following blast overpressure exposure.

Bibliographic

Authors
Qu Y, Chen Q, Chai J, Hu F, Liu TT, Liu X, et al.
Journal
Surgery
Year
2025
PMID
39799761
DOI
10.1016/j.surg.2024.109044

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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