Phenolic antioxidants and prooxidants: are they really so different?
Toxicologist 2001 Mar; 60(1):393
Hydroxy-function of phenolic compounds renders them effective donors of reducing equivalents for radicals providing for their radical scavenging role. The reducing potency of phenolic compounds is also utilized in enzymatic peroxidase-catalyzed reactions. In both cases, the one-electron oxidation intermediate, the phenoxyl radical, determines further pathways through which phenolic compounds participate in cell metabolism. If phenoxyl radicals are not indiscriminately reactive towards biomolecules, they can be selectively reduced by electron transport enzymes or redox cascades to yield antioxidant recycling. The most prominent example of this is the interaction of vitamin E phenoxyl radicals with coenzyme Q, ascorbate and thiols (e.g., dihydrolipoic acid). If the reactivity of phenoxyl radicals is high enough to directly oxidize critical biomolecules (proteins, lipids, nucleic acids), these reactions may overwhelm capacities of protective redox regulation and trigger redox-cycling cascades. The latter can catalytically generate huge amounts of new reactive radicals as exemplified by metabolism of such molecules as phenol and etoposide in myeleperoxidase-rich human leukemia HL60 cells and human epidermal keratinocytes. Thus a high radical scavenging activity of phenolic compounds is a necessary but not sufficient prerequisite for their protective antioxidant role. Detailed studies of the redox reactivity of phenoxyl radicals should be mandatory for antioxidant evaluations.
Phenolic-compounds; Phenols; Antioxidants; Cell-metabolism; Thiols; Antioxidation; Enzymes
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California