Q and A: Is Hydrogen A POWERFUL Antioxidant?

Q and A: Is Hydrogen A POWERFUL Antioxidant?

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“Therefore, logical to conclude that the mechanism of hydroxyl radical scavenging by hydrogen is correct, since the administration of molecular hydrogen seems to alleviate the same harmful damages attributed to the hydroxyl radical. Moreover, the direct scavenging of the hydroxyl radical is currently the only primary direct mode of action that has been postulated, and, as discussed, scavenging of toxic reactive molecules can, in turn, result in changes in both signal transduction and gene expression. However, although the mechanism of direct scavenging by hydrogen is the only one considered to be a primary/direct mode of action, unfortunately, it cannot fully explain all the diverse biological effects of H2 [7]. Moreover, the biological significance of this reaction is debated [108,120,121]. This is partly because the 2nd-order reaction rate constant between hydroxyl radicals and H2 (4.2 × 107 M−1 s−1) is about three orders of magnitude lower than that between other more abundant nucleophilic cellular components [108]. Additionally, the scavenging of the hydroxyl radical would not only produce the inert byproduct of water but also either the highly reactive atomic hydrogen radical or the even more reactive solvated electron (H2 + •OH → H3O+ + e−), each of which could induce oxidative damage as would the hydroxyl radical [122].”

Moreover, H2 is only transiently present in the body, yet its biological and antioxidant effects remain well-after H2 has been cleared from the body [123]. This may suggest that the mechanism may have more to do with signal modulation than direct radical scavenging [108,110]. H2 seems to modulate the expression of diverse genes, including NF-κB, c-Jun N-terminal kinase (JNK), fibroblast growth factor 21 (FGF-21) [124], peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) [125], proliferation cell nuclear antigen, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and many other transcription factors and regulatory proteins [10,126]. However, these molecules are likely downstream or indirectly regulated by H2, as the direct targets of H2 have yet to be elucidated [10].

Taken together, it is clear that although the selective extinctions of hydroxyl radical and peroxynitrite were initially proposed as underlying mechanisms, there must be other explanations [127]. Molecular hydrogen regulates signaling pathways and gene expression via modulating the expression/activities of various biomolecules, as well as several miRNAs, which may account for the therapeutic effects of anti-reperfusion injury, anti-radiation injury, anti-inflammation, anti-apoptosis, anti-metabolic disorders, anti-allergy, anti-dementia as well as anti-aging [7,10].





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