分子状水素による神経保護における循環性メッセンジャーの役割
Molecular hydrogen (H₂) exerts protective effects against a range of oxidative-stress-associated conditions. Beyond its well-characterized direct antioxidant action—namely scavenging of the highly cytotoxic hydroxyl radical (•OH)—evidence indicates that neuroprotection persists even after H₂ is no longer present in the body following chronic administration via drinking water, pointing to indirect signaling mechanisms. In a Parkinson's disease mouse model, approximately 7 days of H₂-water preconditioning produced significant neuroprotection. Mechanistic investigations revealed that H₂ in drinking water stimulates ghrelin production and secretion from the stomach through β1-adrenergic receptor activation. The released ghrelin enters systemic circulation, crosses the blood-brain barrier, and activates the growth-hormone secretagogue receptor in the brain. Upregulation of ghrelin mRNA was also confirmed in the ghrelin-producing cell line SG-1. These findings illuminate the chronic, indirect actions of H₂ and suggest avenues for preventive investigation.
H₂ in drinking water stimulates gastric ghrelin release via β1-adrenergic receptor activation; circulating ghrelin crosses the blood-brain barrier and activates the growth-hormone secretagogue receptor, mediating indirect neuroprotection.
Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).
See also:
https://h2-papers.org/en/papers/31100203