Preconditioning with hydrogen gas produces cardioprotective effects through autophagy activation in rat cardiomyocytes
Year: 2025
Type: article
Abstract: BACKGROUND: It is controversial whether hydrogen (H2) gas can activate cellular survival cascades and autophagy in the myocardium. This translational study aimed to investigate the hypothesis that preconditioning with inhaled H2 gas had a cardio-protective effect mediated through the activation of cellular signaling cascades and autophagy. METHODS: Rat cardiomyocytes were isolated following 3% H2 gas inhalation for 60 min and were then incubated in a solution with or without 10 μM of 3-methyladenine (MA), an autophagy inhibitor. Intracellular Ca2+ concentration after 10-min perfusion of hydrogen peroxide, Ca2+ mobilization from the endoplasmic reticulum (ER), and opening of the mitochondrial permeability transition pore (MPTP) were estimated using fluorescence imaging. The expressions of extracellular signal-regulated kinase (ERK) and Akt and the levels of mitochondrial membrane potentials (ψm) were determined using flow cytometry. Furthermore, autophagosomes and microtubule-associated light chain (LC) 3-II were estimated using for autophagy activation flow cytometry. RESULTS: H2 gas inhalation effectively inhibited the increase in the intracellular Ca2+ concentration and Ca2+ mobilization from the ER. The inhibitory effects of H2 gas were completely abolished by pretreatment with 3-MA. H2 gas inhalation also prolonged the time to MPTP opening, which was considerably shortened by the 3-MA pretreatment. The expression of signaling molecules and the levels of ψm decreased after 1.8 mM Ca2+ stimulation. Regardless of the stimulation, H2 gas inhalation preserved the ERK expression and ψm levels and increased autophagosomes and the LC3-II expression, but it did not affect the Akt expression. The 3-MA pretreatment completely abolished the cardio-protective effects of H2 gas as well as the autophagy activation. CONCLUSIONS: Preconditioning with H2 gas confers the cardio-protective effect in association with the activation of the mitogen-activated protein kinase/ERK pathway and autophagy in the myocardium. Thus, it may be feasible and effective as preventive intervention in patients undergoing cardiac surgery.
Source: BMC Pharmacology and Toxicology
Institution: Osaka Metropolitan University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W4416717413