水素ガス吸入による多菌性敗血症マウスモデルへの保護効果：酸化ストレスおよびHMGB1放出の抑制を介したメカニズム
Sepsis remains a leading cause of mortality in intensive care settings, with excessive reactive oxygen species production central to its pathophysiology. Using a cecal ligation and puncture (CLP) mouse model, this study examined whether H2 gas inhalation could confer protection against sepsis-related organ damage. Inhalation of 2% H2 initiated at 1 or 6 hours post-CLP significantly improved survival in both moderate and severe CLP groups, with effects dependent on concentration and timing. Multiple organ injury markers—including lung myeloperoxidase activity, wet-to-dry weight ratio, bronchoalveolar lavage protein levels, serum biochemical parameters, and histopathological scores—were substantially reduced by H2 inhalation at 24 hours post-CLP. Mechanistically, H2 exposure was associated with decreased oxidative product levels, elevated antioxidant enzyme activities, and lower concentrations of high-mobility group box 1 (HMGB1) in both serum and tissue. These findings suggest that H2 inhalation may offer a protective approach against sepsis-induced organ dysfunction.
H2 selectively scavenges hydroxyl radicals, reducing oxidative damage while enhancing antioxidant enzyme activity. Concurrently, it suppresses the release of HMGB1, a late-phase inflammatory mediator, thereby limiting multi-organ injury in sepsis.
For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.
See also:
https://h2-papers.org/en/papers/19997046