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

Abstract Background Lungs are one of the most common target organs of sepsis [ 1 ]. Hydrogen gas (H 2 ), which has selective anti-oxidative effects, can be effectively used to treat septic mice. Mitochondrial dysfunction and dynamics play important roles in sepsis-induced organ damage. Methods By using cecal ligation and puncture (CLP), a classic septic model, we explored the role of 2% H 2 treatment in sepsis-induced acute lung injury (ALI) linked to mitochondrial function and dynamics. We randomized male Institute for Cancer Research (ICR) mice into 4 groups: sham, sham + H 2 , CLP and CLP + H 2 . At 24 h after CLP or sham operations, we used histological examination and transmission electron microscopy (TEM) to observe lung slices. We analyzed oxygenation index (PaO 2 /FiO 2 ), mitochondrial-membrane potential (MMP), adenosine triphosphate (ATP) levels, respiration control ratio (RCR) and mitochondrial-respiration complex activities (I and II) using commercial kits, and dynamin-related protein 1 (Drp1) and mitofusin-2 (MFN2) using Western blot. Results Therapy with 2% H 2 increased PaO 2 /FiO 2 ratios, MMP and ATP levels, RCR, complex I activity and MFN2 expression but decreased histological score and Drp1 levels in the presence of sepsis. These data indicated that inhalation of 2% H 2 to regulate mitochondrial function and dynamics may be a promising therapeutic strategy for lung injuries induced by severe sepsis.