Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism.

The present study aimed to investigate the impact of hydrogen (H) on chronic intermittent hypoxia (CIH)-induced cardiac hypertrophy in mice by modulating iron metabolism. C57BL/6N mice were randomly allocated into four groups: control (Con), CIH, CIH + H, and H. The mice were exposed to CIH (21-5% FiO, 3 min/cycle, 8 h/d), and received inhalation of a hydrogen-oxygen mixture (2 h/d) for 5 weeks. Cardiac and mitochondrial function, levels of reactive oxygen species (ROS), and iron levels were evaluated. The H9C2 cell line was subjected to intermittent hypoxia (IH) and treated with H. Firstly, we found H had a notable impact on cardiac hypertrophy, ameliorated pathological alterations and mitochondrial morphology induced by CIH ( < 0.05). Secondly, H exhibited a suppressive effect on oxidative injury by decreasing levels of inducible nitric oxide synthase (i-NOS) ( < 0.05) and 4-hydroxynonenal (4-HNE) ( < 0.01). Thirdly, H demonstrated a significant reduction in iron levels within myocardial cells through the upregulation of ferroportin 1 (FPN1) proteins ( < 0.01) and the downregulation of transferrin receptor 1 (TfR1), divalent metal transporter 1 with iron-responsive element (DMT1(+ire)), and ferritin light chain (FTL) mRNA or proteins ( < 0.05). Simultaneously, H exhibited the ability to decrease the levels of Fe and ROS in H9C2 cells exposed to IH ( < 0.05). Moreover, H mediated the expression of hepcidin, hypoxia-inducible factor-1α (HIF-1α) ( < 0.01), and iron regulatory proteins (IRPs), which might be involved in the regulation of iron-related transporter proteins. These results suggested that H may be beneficial in preventing cardiac hypertrophy, a condition associated with reduced iron toxicity.