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Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases

[ Vol. 27 , Issue. 5 ]

Author(s):

Ikuroh Ohsawa*   Pages 659 - 666 ( 8 )

Abstract:


Because multicellular organisms do not have hydrogenase, H2 has been considered to be biologically inactive in these species, and enterobacteria to be largely responsible for the oxidation of H2 taken into the body. However, we showed previously that inhalation of H2 markedly suppresses brain injury induced by focal ischemia–reperfusion by buffering oxidative stress. Although the reaction constant of H2 with hydroxyl radical in aqueous solution is two to three orders of magnitude lower than that of conventional antioxidants, we showed that hydroxyl radical generated by the Fenton reaction reacts with H2 at room temperature without a catalyst. Suppression of hydroxyl radical by H2 has been applied in ophthalmic surgery. However, many of the anti- inflammatory and other therapeutic effects of H2 cannot be completely explained by its ability to scavenge reactive oxygen species. H2 administration is protective in several disease models, and preculture in the presence of H2 suppresses oxidative stress-induced cell death. Specifically, H2 administration induces mitochondrial oxidative stress and activates Nrf2; this phenomenon, in which mild mitochondrial stress leaves the cell less susceptible to subsequent perturbations, is called mitohormesis. Based on these findings, we conclude that crosstalk between antioxidative stress pathways and the anti-inflammatory response is the most important molecular mechanism involved in the protective function of H2, and that regulation of the immune system underlies H2 efficacy. For further medical applications of H2, it will be necessary to identify the biomolecule on which H2 first acts.

Keywords:

Hydroxyl radical, immune system, inflammation, ischemia–reperfusion, mitohormesis, molecular hydrogen, noncommunicable disease, reductant.

Affiliation:

Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology



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