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Hydrogen Gas Protects Against Intestinal Injury in Wild Type But Not NRF2 Knockout Mice With Severe Sepsis by Regulating HO-1 and HMGB1 Release.

重症敗血症マウスにおける水素ガスの腸管保護効果：NRF2ノックアウトモデルによるHO-1およびHMGB1を介したメカニズムの解明

animal study inhalation positive 2%

Abstract

This animal study examined the intestinal effects of 2% H2 gas inhalation in a cecal ligation and puncture (CLP) model of severe sepsis, comparing wild-type (WT) and Nrf2 knockout (KO) mice. In WT animals, H2 inhalation improved 7-day survival, reduced pro-inflammatory cytokines (TNF-α, IL-6, HMGB1), elevated anti-inflammatory IL-10, enhanced antioxidant enzyme activity (superoxide dismutase, catalase), decreased oxidative markers (MDA, 8-iso-PGF2α), and upregulated heme oxygenase-1 (HO-1) expression in serum and intestinal tissue. These protective responses were absent in Nrf2 KO mice, indicating that the Nrf2 transcription factor is essential for H2-mediated intestinal protection. The findings suggest that HO-1 induction and HMGB1 suppression downstream of Nrf2 activation constitute the primary mechanism underlying H2 efficacy in sepsis-associated intestinal injury.

Mechanism

H2 inhalation activates Nrf2, which upregulates HO-1 expression and suppresses HMGB1 release, thereby reducing oxidative stress and inflammatory damage in intestinal tissue. Deletion of Nrf2 abolishes these protective effects, confirming its essential role in the H2-mediated pathway.

Bibliographic

Authors
Yang Y, Bian Y, Li Y, Liu L, Zhang H, Xie K, et al.
Journal
Shock
Year
2017
PMID
28234792
DOI
10.1097/SHK.0000000000000856

Tags

Disease:intestinal injury (54) sepsis (48) Mechanism:antioxidant enzymes (423) apoptosis regulation (280) anti-inflammatory (743) Nrf2 pathway (106) 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.

See also:

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