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

被引:422
作者
Metodiewa, D
Jaiswal, AK
Cenas, N
Dickancaité, E
Segura-Aguilar, J
机构
[1] Univ Stockholm, Wallenberg Lab, Dept Biochem, Biochem Toxicol Unit, S-10691 Stockholm, Sweden
[2] Lodz Tech Univ, Inst Appl Radiat Chem, PL-93590 Lodz, Poland
[3] Dept Biochem, Vilnius, Lithuania
[4] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA
基金
瑞典研究理事会;
关键词
quercetin; oxidation; semiquinone radicals; o-quinone; reduction; cell culture; viability; free radical;
D O I
10.1016/S0891-5849(98)00167-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 underlying this undesirable ability seems to involve its metabolic oxidoreductive activation. Based on the structural properties of quercetin, we have investigated 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 indeed the products of enzymatically catalyzed oxidative degradation of quercetin. The former radical might serve to facilitate the formation of superoxide and depletion of GSH, which could confer a specificity of its prooxidative action in situ. The observed one-electron reduction of o-quinone may enrich 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 monolayer cell cultures. The results are indicative of the intracellular metabolic activation of quercetin to o-quinone, the process which can be partially associated with the observed concentration-dependent cytotoxic effect of quercetin. (C) 1998 Elsevier Science Inc.
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页码:107 / 116
页数:10
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