How Do Nutritional Antioxidants Really Work: Nucleophilic Tone and Para-Hormesis Versus Free Radical Scavenging in vivo

By H. Forman, K. Davies, F. Ursini. Free Radical Biology & Medicine, 2013

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We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of non-radical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of ‘Nucleophilic Tone,’ by a mechanism that can be called ‘Para-Hormesis,’ provides a means for regulating physiological non-toxic concentrations of the non-radical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health.

Subfields: Biochemistry, Molecular Biology, Organic Chemistry

View Paper: https://www.semanticscholar.org/paper/36661381f1b4893fe156f7550c9cbd76a0414eb7

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In Molecular Biology

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