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How do nutritional antioxidants really work: Nucleophilic tone and para-hormesis versus free radical scavenging in vivo
Open accessAbstract
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.
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Metadata
- Authors
- Forman, H. J., Davies, K. J. A., & Ursini, F.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 66
- Pages
- 24-35
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2066472053
- Cited by
- 703
- References
- 14
- FWCI
- 21.65
- Type
- journal article
- Language
- en
- Open access
- green
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