Elsevier

Toxicology

Volume 177, Issue 1, 1 August 2002, Pages 67-80
Toxicology

Plant phenolic antioxidant and prooxidant activities: phenolics-induced oxidative damage mediated by metals in plants

https://doi.org/10.1016/S0300-483X(02)00196-8Get rights and content

Abstract

Plant phenolic compounds such as flavonoids and lignin precursors are important constituents of the human diet. These dietary phytophenolics have been recognized largely as beneficial antioxidants that can scavenge harmful active oxygen species including O2radical dot, H2O2, radical dotOH, and 1O2. Here we review our current understanding of the antioxidant and prooxidant actions of phenolics in plant cells. In plant systems, phytophenolics can act as antioxidants by donating electrons to guaiacol-type peroxidases (GuPXs) for the detoxification of H2O2 produced under stress conditions. As a result of such enzymatic as well as non-enzymatic antioxidant reactions, phenoxyl radicals are formed as the primary oxidized products. Until recently, phenoxyl radicals had been difficult to detect by static electron spin resonance (ESR) because they rapidly change to non-radical products. Application of Zn exerts spin-stabilizing effects on phenoxyl radicals that enables us to analyze the formation and decay kinetics of the radicals. The ESR signals of phenoxyl radicals are eliminated by monodehydroascorbate radical (MDA) reductase, suggesting that phenoxyl radicals, like the ascorbate radical, are enzymatically recycled to parent phenolics. Thus, phenolics in plant cells can form an antioxidant system equivalent to that of ascorbate. In contrast to their antioxidant activity, phytophenolics also have the potential to act as prooxidants under certain conditions. For example, flavonoids and dihydroxycinnamic acids can nick DNA via the production of radicals in the presence of Cu and O2. Phenoxyl radicals can also initiate lipid peroxidation. Recently, Al, Zn, Ca, Mg and Cd have been found to stimulate phenoxyl radical-induced lipid peroxidation. We discuss the mechanism of phenoxyl radical prooxidant activity in terms of lifetime prolongation by spin-stabilizing agents.

Introduction

Plant phenolic compounds such as flavonoids and lignin precursors are potent antioxidants. Vitamin C (ascorbate) functions as a ubiquitous antioxidant in both animals and plants by scavenging reactive oxygen species via enzymatic and non-enzymatic reactions. The concept that flavonoids are efficient antioxidants is not a novel idea itself but has a long research history. In 1937, Szent-Györgyi, a Nobel prize winner who isolated ascorbate, demonstrated that the flavonoid hesperidine can behave similar to ascorbate in maintaining capillary permeability (Bentsáth et al., 1937). Based on this observation he proposed that flavonoids are essential human nutrients, i.e. the short-lived vitamin P (permeability) concept (Bentsáth et al., 1937). Although the vitamin concept of flavonoids did not gain broad acceptance, the idea that flavonoids can complement the functions of ascorbate has renewed interest in the antioxidant hypothesis. After the recent explosion of research in the pharmacology of food phytochemicals, a great number of reports have established that plant phenolic compounds including flavonoids are potent antioxidants with reported antimutagenic and anticarcinogenic effects (Middleton and Kandaswami, 1994, Rice-Evans et al., 1997).

There have also been a number of reports suggesting that dietary phenolics exhibit prooxidant and cytotoxic properties under certain conditions (Summers and Felton, 1994, Yamanaka et al., 1997, Sugihara et al., 1999). The antioxidant/prooxidant activity of phytophenolics can depend on such factors as metal-reducing potential, chelating behavior, pH, and solubility characteristics (Decker, 1997). In this review, we describe how plant phenolics may act as antioxidants or prooxidants in plant cells from the point of view of phenoxyl radical lifetime prolongation.

Section snippets

Biosynthesis of phytophenolics

Phenolics are chemical compounds characterized by at least one aromatic ring (C6) bearing one or more hydroxyl groups. Hydroxycinnamic acids (HCAs) and flavonoids have the basic carbon skeletons C6–C3 and C6–C3–C6, respectively. HCAs and flavonoids are produced from phenylalanine, via the shikimate pathway, general phenylpropanoid pathway and specific flavonoid pathway. Fig. 1 summarizes biosynthetic relationships and basic structures of HCAs and flavonoids.

Flavonoids commonly accumulated in

Stress protectant function of phytophenolics

Most plants constitutively synthesize phenylpropanoids including flavonoids and HCAs. However, accumulation of phenolics in plants can be induced by abiotic and biotic stresses, e.g. UV (ultra violet) radiation, high-light illumination, low temperatures, wounding, low nutrients, and pathogen attack (Dixon and Paiva, 1995, Yamasaki et al., 1995). Abiotic stress has been postulated to promote production of harmful active oxygen species within the cells (Alscher et al., 1997, Draper, 1997). In

Involvement of phenolics in defense mechanisms

Polyphenols, particularly flavonoids and tannins, have long been associated with plant defense against herbivores. We have recently found that in fronds of the aquatic fern Azolla anthocyanin levels negatively correlate with palatability, and that accumulation of anthocyaninis occurs in response to long-term feeding by tadpoles (Cohen et al., 2002). Similar increases in phenolics have also been observed in poplar and oak trees in response to feeding and wounding (Hammerschmidt and Schultz, 1996

Concluding remarks

Reduced forms of phytophenolics are powerful antioxidants equivalent to ascorbate. In contrast, the phenoxyl radical produced through antioxidative reactions and in lignin biosynthesis, is a potential prooxidant. Under normal growth conditions phenoxyl radicals usually do not show harmful prooxidant activity because they are rapidly changed to non-radical products by polymerization reactions or enzymatic (as well as non-enzymatic) reduction of the radicals. However, phenoxyl radicals would

Acknowledgements

This work was supported by fellowships from the Japan Society for the Promotion of Science (JSPS) to Y.S. and M.F.C and by the Grant-in-Aid for Scientific Research (B) and (C) from JSPS to H.Y.

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