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Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics.

敗血症誘発性急性肺傷害に対する水素ガス吸入の保護効果：ミトコンドリア機能および動態の調節を介したメカニズム

Abstract

Using a cecal ligation and puncture (CLP) mouse model, this study examined the effects of 2% hydrogen gas inhalation on sepsis-induced acute lung injury (ALI) in male ICR mice divided into four groups: sham, sham plus H2, CLP, and CLP plus H2. At 24 hours post-operation, histological examination and transmission electron microscopy were performed. Compared with the CLP-only group, hydrogen gas inhalation significantly elevated the oxygenation index (PaO2/FiO2), mitochondrial membrane potential, ATP levels, respiration control ratio, complex I activity, and mitofusin-2 (MFN2) expression. Concurrently, histological injury scores and dynamin-related protein 1 (Drp1) levels were reduced. These findings indicate that 2% H2 inhalation can restore mitochondrial bioenergetics and shift the fission-fusion balance toward fusion, thereby conferring protection against sepsis-associated pulmonary damage.

Mechanism

H2 inhalation suppresses Drp1-mediated mitochondrial fission while upregulating MFN2-driven fusion, thereby restoring mitochondrial membrane potential, ATP synthesis, and respiratory complex I activity in septic lung tissue.

Bibliographic

Authors

Dong A, Wang Y, Li CY, Chen H, Bian Y, Zhang P, et al.

Journal

Int Immunopharmacol

Year

2018

PMID

30380511

DOI

10.1016/j.intimp.2018.10.012

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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