H2-O2 mixture inhalation significantly ameliorates cardiac dysfunction and myocardial pathological changes induced by chronic intermittent hypoxia through multiple mechanisms including suppression of endoplasmic reticulum stress-induced apoptosis, inhibition of MAPK signaling pathways, and reduction of reactive oxygen species via enhanced antioxidant enzyme expression. These findings suggest that hydrogen therapy may represent a novel therapeutic approach for mitigating cardiac injury associated with obstructive sleep apnea and other hypoxic conditions.
Plain-Language Summary
This study used rats to model obstructive sleep apnea (a condition where breathing repeatedly stops during sleep), which causes the heart to be exposed to low oxygen levels. Researchers gave some rats a mixture of hydrogen and oxygen gas to breathe for 35 days and found that this treatment improved heart function and reduced damage to heart tissue. The treatment appeared to work by reducing harmful molecules called reactive oxygen species and preventing cells from dying through a process called apoptosis (programmed cell death).
Abstract
Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O2 (FiO2) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H2-O2 mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H2-O2 mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H2-O2 mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H2-O2 mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H2-O2 mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H2-O2 mixture significantly reduced ER stress and apoptosis and that H2 might be an efficient antioxidant against the oxidative stress injury induced by CIH.
DOI: 10.1155/2019/7415212
