H₂ Papers

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Hydrogen gas reduces HMGB1 release in lung tissues of septic mice in an Nrf2/HO-1-dependent pathway.

敗血症マウスの肺組織におけるHMGB1放出に対する水素ガスの抑制効果：Nrf2/HO-1経路を介したメカニズムの検討

animal study inhalation positive 2%

Abstract

Using a cecal ligation and puncture (CLP) sepsis model in wild-type and Nrf2-knockout ICR mice, the effects of 2% H2 gas inhalation (60 min at 1 h and 6 h post-surgery) on lung injury were examined. In wild-type animals, H2 inhalation improved 7-day survival, reduced the lung wet/dry weight ratio and histopathological injury scores, lowered pro-inflammatory mediators (TNF-α, IL-6, HMGB1), elevated the anti-inflammatory cytokine IL-10, enhanced antioxidant enzymes (SOD, CAT, HO-1), and decreased the oxidative marker MDA. These protective outcomes were absent in Nrf2-knockout mice, indicating that Nrf2 is essential for H2-mediated upregulation of HO-1 and downregulation of HMGB1, thereby attenuating sepsis-induced pulmonary damage.

Mechanism

H2 gas activates Nrf2, which upregulates HO-1 expression and suppresses HMGB1 release, leading to reduced oxidative stress and pro-inflammatory cytokine levels that collectively mitigate sepsis-induced lung injury.

Bibliographic

Authors
Yang Y, Yang M, Wang CY, Xie K, Yu Y
Journal
Int Immunopharmacol
Year
2019
PMID
30660872
DOI
10.1016/j.intimp.2019.01.022

Tags

Disease:sepsis (48) Delivery:inhalation delivery (196) Mechanism:antioxidant enzymes (423) apoptosis regulation (280) hydroxyl radical scavenging (352) anti-inflammatory (743) Nrf2 pathway (106) oxidative stress (899)

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.

See also:

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