Molecular Hydrogen Attenuates High Hydrostatic Pressure-Induced Neuronal Cell Damage by Reversing Dysfunction of Mitochondrial Electron Transfer Chain

Cellular hydrostatic pressure beyond its normal range can induce the accumulation of reactive oxidative species (ROS) generated by mitochondria and lead to pathological conditions such as glaucomatous optic neuropathy. However, little is known about how the mitochondrial electron transfer chain (ETC) is affected by elevated pressure. Moreover, the protective effects of hydrogen on various pathological conditions have been observed by reductions in ROS, yet the role of hydrogen in high hydrostatic pressure (HHP)-induced cell damage remains obscure. The goal of this study was to investigate the effect of HHP on ETC activity and whether hydrogen exerts protective effects against HHP-induced damage in cultured neuronal cells. Cultured SH-SY5Y human neuroblastoma cells were exposed to an elevated ambient hydrostatic pressure of 50 mmHg for a period of 2 to 6 h. HHP impaired the activities of ETC complexes, and these effects were reversed by hydrogen. Significant increases in apoptotic rates and intracellular ROS levels were observed in HHP-treated SH-SY5Y cells. Hydrogen significantly inhibited the apoptotic rates and reduced the levels of ROS. These findings suggest that HHP induces cell damage by causing ETC dysfunction to increase oxidative stress and that hydrogen may act as a protective agent to alleviate HHP-induced neuronal injury.