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Dietary Flavonoids, their Toxicity and Influence on Detogyfing System

Flavonoids are phytochemicals exhibiting a wide range of biological activities, among which are antioxidant activity, the ability to modulate activity of several enzymes or cell receptors and possibility to interfere with essential biochemical pathways. Some of them can induce point mutations as well. We have examined five flavonoids, three structurally related flavons (quercetin, fisetin, and myricetin) one flavonol (luteolin) and one glycosilated flavanone (naringin) for their (a) ability to inhibit mitochondrial dehydrogenases as an indicator of cytotoxic effect, (b) influence on cell membrane permeability (lactate dehydrogenase permeability) ; (c) influence on intracellular level of glutathione, and (e) effect on expression of cytochrome CYP1A1. In this study human cervical carcinoma parental HeLa cells were used and their drug-resistant subline (HeLa CK). Toxicity of investigated flavonoids was similar in both cell lines. Only quercetin and luteolin have caused induction of glutathione in HeLa CK cell line, while in HeLa cell line glutathione was not inducible. Myricetin, quercetin and luteolin have caused increased GSTs activity in HeLa cell line, and activity of GSTs in HeLa CK cell line was increased after treatment with all examined flavonoids. Basal level of cytochrome 1A1 was higher in in resistant, HeLa CK cell line. Quercetin, fisetin and luteolin have caused induction of CYP 1A1 expression. In resistant HeLa CK cell line only luteolin has caused slight repression of CYP 1A1 expression. Other flavonoids did not influence on CYP 1A1 expression. In conclusion, small differences in chemical structure of flavonoids lead to drastic change of their biological effects. These effects are strongly dependent of cell type as well as test systems used. Extensive studies on structure-function relationship of flavonoids in different test systems could provide rational approach to drug and chemopreventive agent design.

flavonoids; detoxyfing systems phase I and II; antioxidant/prooxidant; apoptosis; cervical carcinoma cells

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