Indirect antioxidants

Dinkova-Kostova, AT and Talalay, P, 2008. Direct and indirect antioxidant properties of inducers of cytoprotec-tive proteins, Mol Nutr Food Res 52 Suppl, S128-S138. 

Induction of phase II enzymes, which conjugate reactive electrophiles and act as indirect antioxidants, appears to be the means for achieving protection against a variety of carcinogens in animals and humans. Transcriptional control of the expression of these enzymes is mediated, at least in part,... 

The antioxidant system in humans is a complex network composed by several enzymatic and nonenzymatic antioxidants. In addition to being an antioxidant, lycopene also exerts indirect antioxidant properties by inducing the production of cellular enzymes such as superoxide dismutase, glutathione S-transferase, and quinone reductase that also protect cells from reactive oxygen species and other electrophilic molecules (Goo and others 2007). 

Figure 29.17). The first mechanism is untypical one for classical antioxidants and probably may be considered as a novel mode of antioxidant activity. The second one is typical for indirect antioxidants. 

NADPH might be considered as an indirect antioxidant due to its function as the reductant of various oxidized substrates, for example in the re-reduction of GSSG into GSH. However, it has recently been shown [1] that NADPH possesses the free radical scavenging activity reacting with such free radicals as CO/, N02 ROO and R0 . It should be noted that the efficiency of NADPH may increase under in vivo conditions due to its regeneration by numerous enzymes. 

We observed PKC-like activity in mouse forestomach extract (29). The activity was activated by TPA plus phosphatidylserine in the absence of calcium. Protein associated with this activity waspartially-puriEedby DEAE-cellulose chromatogrs hy. In mice pretreated with CLA 24 hours prior to sacrifice, the PKC-like activity was refractory to activation by TPA and phosphatidylserine. This observation indicates that cis-9, trans-11 incorporated into phospholipid might directly affect the interaction of TPA with PKC. Further, since PKC controls superoxide generation 30 CLA might in this way serve as an indirect antioxidant. 

In addition to their direct antioxidant activity, ferulic acid and its ester derivatives have also been shown to act as indirect antioxidants, that is, to induce cytoprotective (phase 2) enzymes [Dinkova-Kostova et al., 1998 Dinkova-Kostova, 2002], Similarly to curumin, ferulic acid derivatives also... 

Antioxidants represent a very large category of products because many chemical entities may have direct or indirect antioxidant activity. 

The mechanism of melatonin s interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through a radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4, and C7 and nitrosation [169]. The mechanisms by which melatonin protects against LP most likely involve direct or indirect antioxidant and free-radical scavenging activities of this indoleamine [169,171]. 2-Phenyl indole derivatives have redox properties because of the presence of an electron-rich aromatic ring system that allows the indoleamine to easily function as an electron donor. For these derivatives, the possible antioxidant mechanism might be most probably toward carbon-centered radicals described by Antosiewicz et al. [172]. 

Thus, re-examination of metal-chelating agents, classical indirect antioxidants, is warranted. NFT and senile plaques have been shown to contain redox-active transition metals (Smith et al., 1997a Sayre et al., 2000) and may exert pro-oxidant... 

Gao, X., Dinkova-Kostova, A. T., and Talalay, P. (2001) Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage the indirect antioxidant effects of sulforaphane. Proc. Natl Acad. Sci. USA 98, 15221-15226. 

In view of their reduction potential, flavonoids have also been shown to interact with enzymes either unspecifically or specifically and modify their activity through reduction of metals in the active center. Of particular interest, because of their role in inflammatory conditions, is the reductive inactivation of lipoxygenases, cyclo-oxygenases, myeloperoxidase, and xanthine oxidase. In view of prooxidant activity of the enzymes, their inhibition by polyphenols may be regarded as an indirect antioxidation action. The list of enzymatic activities inhibited by flavonoids and other polyphenols also include phospholipase A2, protein kinases, metalloproteinases, drug metabolism enzymes, and telomerase, as reviewed elsewhere (Frade et al, 2005). 

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