Title : Basic and clinical research on hydrogen therapy for sepsis
Abstract:
We have established ourselves as one of the leading researchers exploring the therapeutic potential of molecular hydrogen (H?) in critical care and perioperative medicine. Our research spans experimental animal models, mechanistic studies, and early clinical investigations, with particular focus on sepsis, multiple organ dysfunction, and perioperative neuroprotection.
A major theme of our work is the role of hydrogen in sepsis and multiple organ injury. In classic sepsis models such as cecal ligation and puncture, lipopolysaccharide administration, and zymosan challenge, our group demonstrated that inhaled hydrogen significantly improves survival, reduces systemic inflammation, and preserves the function of key organs including the heart, lung, liver, kidney, intestine, and brain. One of his hallmark contributions is the demonstration that hydrogen therapy can prevent or mitigate sepsis-associated encephalopathy (SAE), a devastating complication leading to long-term cognitive impairment. Our studies showed that high-concentration hydrogen inhalation (around 67%) not only improved survival but also preserved learning and memory, reduced tau phosphorylation, and improved neuronal mitochondrial health.
Mechanistic investigations provide strong insights into how hydrogen confers these protective effects. The author and colleagues consistently highlight the Nrf2/HO-1 signaling pathway as a central mediator of hydrogen’s antioxidant and cytoprotective functions. By enhancing endogenous antioxidant defenses, hydrogen reduces oxidative stress, lipid peroxidation, and cell death. Equally important are its effects on mitochondrial dynamics and quality control. Our studies reveal that hydrogen helps restore the balance between mitochondrial fission and fusion, promotes mitochondrial biogenesis, and facilitates PINK1/Parkin-mediated mitophagy. These processes ensure removal of damaged mitochondria and maintenance of cellular energy metabolism, thereby improving organ resilience during systemic inflammation. Another novel mechanistic finding is the inhibition of the cGAS-STING-IRF3 pathway, a central driver of innate immune activation, suggesting that hydrogen exerts anti-inflammatory effects by modulating cytosolic DNA sensing.
In conclusion, our body of research offers compelling preclinical and early clinical evidence that molecular hydrogen is a safe and promising adjunctive therapy in critical care and anesthesiology. Our studies collectively demonstrate that hydrogen protects multiple organs in sepsis, preserves cognitive function by maintaining mitochondrial health, and reduces postoperative complications in surgical patients. The mechanistic insights into Nrf2/HO-1 signaling, mitochondrial dynamics, mitophagy, and innate immune modulation provide a strong scientific foundation for clinical translation. As the field of hydrogen medicine advances, our contributions are likely to play a pivotal role in shaping its integration into modern critical care practice.
