Effects of quercetin on drug metabolizing enzymes and oxidation of 2', 7-dichlorofluorescin in HepG2 cells

Abstract

1 The effects of quercetin on drug metabolising enzymes and oxygen radicals were studied in human HepG2 cells. 2 Cytotoxicity of quercetin in HepG2 cells was seen at 50 μM and above as evaluated by lactate dehydrogen ase (LDH) leakage, neutral red (NR) uptake, and 3-(4,5- dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bro mide (MTT) reduction. 3 Quercetin inhibited activity of human cytochrome P- 450 towards ethoxycoumarin and ethylresorufin at relatively low substrate concentrations (0.1 μM and above). 4 In comparison to induction by the positive control (β- naphthoflavone; 1.0 μM), quercetin did not signifi cantly induce the metabolism of ethoxycoumarin or glutathione-S-transferase (GST) protein or activity. 5 Response elements for human CYP1A1, GSTλa, xenobiotic response element (XRE), fos, HSP70, CRE, p53, NFκB and DNA damage (GADD) in HepG2 cells were not activated by quercetin. 6 Quercetin exhibited antioxidant activity in HepG2 cells as evidenced by its ability to inhibit the oxidation of the fluorochrome dichlorofluorescin. 7 The results indicate a range of potential beneficial effects of quercetin with respect to the influence on carcinogen-metabolising enzymes, scavenging of re active oxygen species and a lack of stress response in HepG2 cells.