Hydrogen-rich gas therapy significantly enhances mitochondrial recovery following ischemia-reperfusion injury by restoring mitochondrial membrane potential, increasing ATP production, and reducing reactive oxygen species while suppressing pro-apoptotic signaling. By modulating upstream hypoxia-driven pathways (HIF1α and PDK1), H2 therapy demonstrates therapeutic potential for treating ischemia-reperfusion injuries and other hypoxia-related conditions affecting intestinal and potentially other tissues.
Plain-Language Summary
Researchers exposed intestinal cells to conditions mimicking lack of oxygen and blood flow (ischemia-reperfusion injury), then treated some cells with hydrogen-rich gas during recovery. Hydrogen treatment helped cells restore their mitochondria (the energy-producing structures in cells), produce more energy (ATP), and reduce harmful molecules called reactive oxygen species. The hydrogen also prevented cells from dying and appeared to work by affecting genes related to low-oxygen stress.
Abstract
Background: Ischemia-reperfusion (I/R) injury induces oxidative stress, leading to damage in highly susceptible intestinal tissues. Molecular hydrogen (H2) has shown therapeutic potential in I/R injuries, with our prior research showing its efficacy in improving outcomes in rat intestinal transplantation models. However, its impact on mitochondrial function remain insufficiently understood. This study aims to elucidate how H2 modulates mitochondrial function impaired by I/R injury. Methods: To assess the effects of H2 on I/R injury, cells were divided into three groups: a control group, a hypoxic group (99 % N2, 1 % O2, without H2 for 3, 6, or 24 h), and a hypoxic-H2 group (99 % H2, 1 % O2, for the same durations). After treatment, cells were reoxygenated under normoxic conditions (21 % O2) for 1, 2, 4, or 6 h. Mitochondrial membrane potential, oxygen consumption, and ATP production were measured. Reactive oxygen species production and apoptotic and metabolic regulators were also assessed. Results: H2 markedly promoting mitochondrial recovery following I/R injury, by enhancing ATP production, restoring mitochondrial membrane potential, and improving oxygen consumption. It also reduced ROS levels and suppressed pro-apoptotic signaling. Notably, H2 suppressed the expression of HIF1α and PDK1, suggesting that H2 may act upstream of hypoxia-driven signaling pathways. These changes promoted oxidative phosphorylation and overall cellular function during reperfusion. Conclusions: Our findings reveal that H2 therapy supports mitochondrial function, suppresses ROS, and modulates hypoxia-driven pathways in I/R injury. These insights advance the understanding of H2's potential in addressing I/R injury and provide a foundation for its application in other hypoxia-related conditions.
