Quercetin may act as a cytotoxic prooxidant after its metabolic activationto semiquinone and quinoidal product

In the last ten years, there has been an important increase in interest in quercetin action as a unique antioxidant, but its putative role in numerous prooxidant effects is also being continually updated. The mechanism underl ying this undesirable ability seems to involve its metabolic oxidoreductive activation. Based on the structural properties of quercetin, we have inves tigated whether its catechol moiety may be the potential tool for revealed toxicity. We demonstrated, with an ESR spin-stabilization technique coupled to conventional spectrophotometry, that o-semiquinone and o-quinone are in deed the products of enzymatically catalyzed oxidative degradation of querc etin. The former radical might serve to facilitate the formation of superox ide and depletion of GSH, which could confer a specificity of its prooxidat ive action in situ. The observed one-electron reduction of o-quinone may en rich the semiquinone pool, thereby magnifying its effect. The two-electron reduction of quinone can result in constant resupply of quercetin in situ, thereby also modulating another pathway of its known biological activities. We have also tried to see whether the intracellular oxidative degradation of quercetin can be confirmed under the controlled conditions of model mono layer cell cultures. The results are indicative of the intracellular metabo lic activation of quercetin to o-quinone, the process which can be partiall y associated with the observed concentration-dependent cytotoxic effect of quercetin. (C) 1998 Elsevier Science Inc.