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Inhalation of H/O(66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage.

H₂/O₂(66.7%/33.3%)吸入による糖尿病合併うつ病マウスの抑うつ様行動抑制:炎症抑制と海馬保護を介したメカニズム

animal study inhalation positive 66.7%

Abstract

Diabetes mellitus complicated with depression (DD) is a psychosomatic condition associated with cognitive impairment and elevated disability risk. Using a mouse model induced by intraperitoneal streptozotocin (150 mg/kg) and lipopolysaccharide (0.5 mg/kg), this study examined the effects of H2/O2 (66.7%/33.3%) inhalation administered for 7 consecutive days. Standard behavioral tests revealed marked reduction in depressive-like behaviors. ELISA measurements showed decreased inflammatory cytokine concentrations in both peripheral serum and hippocampal tissue. MRI and immunofluorescence analyses demonstrated recovery of hippocampal volume and suppression of A1 astrocyte activation. These findings indicate that H2/O2 inhalation exerts beneficial effects on DD-related behavioral and neuroinflammatory endpoints in this preclinical model.

Mechanism

H2 acts as a selective hydroxyl radical scavenger, reducing inflammatory cytokine levels in serum and hippocampal tissue while suppressing A1 astrocyte activation, thereby preserving hippocampal structural integrity in DD mice.

Bibliographic

Authors
Fan H, Shi Y, Liu H, Zuo X, Yang Y, Yin H, et al.
Journal
Biomed Pharmacother
Year
2024
PMID
39405908
DOI
10.1016/j.biopha.2024.117559

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.

→ 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.

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