Coral calcium hydride promotes peripheral mitochondrial division and reduces AT-II cells damage in ARDS via activation of the Trx2/Myo19/Drp1 pathway.
Summary
In LPS-induced ARDS mice, coral calcium hydride (CCH) improved survival comparably to hydrogen gas, reduced lung hemorrhage and edema, and enhanced pulmonary function and microcirculation. Mechanistically, CCH activated Trx2 and the Myo19/Drp1 axis to promote peripheral mitochondrial division in AT-II cells, mitigating oxidative stress and mitochondrial dysfunction.
Key Findings
- CCH improved survival in LPS-induced ARDS mice to a degree comparable with hydrogen inhalation and outperformed untreated controls.
- CCH reduced pulmonary hemorrhage and edema and improved pulmonary function and local microcirculation.
- CCH activated Trx2/Myo19/Drp1 signaling, promoting peripheral mitochondrial division in AT-II cells and reducing oxidative stress and mitochondrial dysfunction.
Clinical Implications
Solid hydrogen carriers like CCH may circumvent safety issues of gas inhalation and offer a mitochondria-targeted adjunct for ARDS; requires dosing, safety, and multi-etiology validation.
Why It Matters
Proposes a practical, potentially safer hydrogen delivery strategy with defined mitochondrial mechanisms that could be translated to ARDS therapy.
Limitations
- Single-etiology (LPS) mouse model; human safety, pharmacokinetics, and dosing remain unknown.
- Long-term outcomes and off-target effects of CCH were not addressed.
Future Directions
Assess pharmacokinetics, safety, and dosing of CCH; validate across multiple ARDS models and large animals; explore combination with lung-protective ventilation.
Study Information
- Study Type
- Basic/Mechanistic Research
- Research Domain
- Treatment
- Evidence Level
- V - Preclinical mouse model study with mechanistic assays; no human clinical data.
- Study Design
- OTHER