分子状水素の直接標的と多機能発現経路：ラジカル反応への介入を中心としたレビュー
Molecular hydrogen (H₂) was historically considered biologically inert in mammalian systems, but subsequent research established its antioxidant capacity and a broad range of additional functions, including anti-inflammatory, anti-allergic, autophagy-regulatory, and energy-metabolic effects. Because H₂ does not readily react with most biomolecules in the absence of a catalyst, identifying its direct molecular targets is critical. This review systematically examines the cascade initiated by H₂ reacting with strong oxidants such as hydroxyl radicals (•OH) in vivo. Suppression of the resulting free radical chain reaction reduces lipid peroxides and their end products; 4-hydroxy-2-nonenal derived from these peroxides upregulates the multifunctional coactivator PGC-1α. Additionally, H₂ modifies oxidized phospholipids, which may antagonize Ca²⁺-channels, thereby inactivating NFAT and CREB transcription factors—a mechanism proposed to underlie H₂ multi-functionality. Potential roles of NFAT in COVID-19, Alzheimer's disease, and advanced cancer are discussed, along with unresolved questions regarding LPS signaling, MAPK, NF-κB pathways, and the Nrf2 paradox. A novel hypothesis involving H₂-induced structural protein changes via hydration-shell alterations is also introduced.
H₂ reacts with hydroxyl radicals to suppress free radical chain reactions, reducing lipid peroxides; the resulting 4-HNE upregulates PGC-1α. Separately, H₂ modifies oxidized phospholipids to antagonize Ca²⁺-channels, inactivating NFAT and CREB transcription factors and thereby mediating its diverse biological effects.
The delivery route is not clearly identifiable from this paper. For hydrogen intake, inhalation is the most efficient route; inhalation, however, carries explosion risk (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/32767925