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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

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

Delivery context

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.

Safety notes

See also:

• Inhalation concentration and LFL / UFL
• Consumer Affairs Agency accident cases
• LFL / UFL terminology
• Inhalation safety threshold lineage

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