Combination therapy with molecular hydrogen and hyperoxia in a murine model of polymicrobial sepsis.
多菌性敗血症マウスモデルにおける水素ガスと高濃度酸素の併用効果
Abstract
Using a cecal ligation and puncture (CLP) murine sepsis model, this study examined the effects of 2% H2 inhalation, 98% hyperoxia, and their combination. In moderate CLP mice, each intervention alone raised 14-day survival from 40% to 80% or 70%, respectively, while the combined approach achieved 100% survival. In severe CLP, 7-day survival improved from 0% to 70% with combination. Organ injury markers in lung, liver, and kidney were reduced, accompanied by lower oxidative stress indicators (8-iso-prostaglandin F2α) and pro-inflammatory cytokines (HMGB1, TNF-α), alongside elevated antioxidant enzyme activities (superoxide dismutase, catalase) and the anti-inflammatory cytokine interleukin-10. These findings indicate that concurrent H2 and hyperoxia administration produces additive protective effects through both antioxidant and anti-inflammatory mechanisms.
Mechanism
H2 selectively scavenges reactive oxygen species, reducing oxidative stress markers. Combined with hyperoxia, it further elevates superoxide dismutase and catalase activities while suppressing pro-inflammatory mediators HMGB1 and TNF-α and increasing IL-10, resulting in enhanced multi-organ protection.
Bibliographic
- Authors
- Xie K, Fu W, Xing W, Li A, Chen H, Han H, et al.
- Journal
- Shock
- Year
- 2012
- PMID
- 23160520
- DOI
- 10.1097/SHK.0b013e3182758646
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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