High concentration of hydrogen gas alleviates Lipopolysaccharide-induced lung injury via activating Nrf2 signaling pathway in mice.
高濃度水素ガス吸入によるLPS誘発急性肺傷害の軽減とNrf2シグナル経路の関与
Abstract
The lung is among the earliest organs to sustain damage during sepsis. This study examined whether inhalation of 67% high-concentration hydrogen (HCH) could reduce acute lung injury (ALI) induced by lipopolysaccharide (LPS) aerosol in mice, and whether the Nrf2 signaling pathway mediates this effect. HCH was administered for 1 hour at 1 and 6 hours post-LPS exposure. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 4 and 24 hours. Histological scores, wet/dry weight ratios, myeloperoxidase (MPO) activity, BALF protein and cytokine levels, caspase-3 activity, TUNEL-positive cell counts, and Nrf2/NF-κB expression were measured in both wild-type and Nrf2-knockout mice. HCH inhalation markedly reduced pathological lung damage, inflammatory cytokine levels, MPO activity, and apoptotic cell counts. Critically, these protective effects were absent in Nrf2-knockout animals, indicating that Nrf2 activation is essential for HCH-mediated protection against LPS-induced ALI.
Mechanism
HCH inhalation activates the Nrf2 signaling pathway, which in turn suppresses NF-κB-mediated pro-inflammatory cytokine production and caspase-3-dependent apoptosis, thereby reducing LPS-induced pulmonary damage.
Bibliographic
- Authors
- Sun R, Zhao N, Su Y, Zhang JH, Wang Y, Yu Y, et al.
- Journal
- Int Immunopharmacol
- Year
- 2021
- PMID
- 34634688
- DOI
- 10.1016/j.intimp.2021.108198
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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