In recent years, the consumption and use of dietary supplements containing concentrated phytochemicals (e.g. flavonoids) increased dramatically. Flavonoids, as foreign compounds (xenobiotics), have great potential to modulate the activity of cytochrome P450s (CYPs), xenobiotic-metabolizing enzymes involved in the activation and detoxification of food and environmental carcinogens. Thus, the aim of this study was to investigate the effects of model glycosylated and deglycosylated flavonoids on CYPs in rat liver and small intestine, as the two main organs responsible for xenobiotic metabolism, after p.o. administration by gastric gavages. The effects of two glycosylated flavonoids (isoquercitrin, rutin) and their aglycone (quercetin) on CYPs were determined using Western blotting technique and specific activity assays with alkyl-resorufin derivatives. In liver microsomes, a considerable increase of all the measured marker activities (EROD, MROD, PROD) was observed only after isoquercitrin treatment. To evaluate the effects of flavonoids on CYPs along small intestine, the tissue was dissected into proximal (near pylorus), middle and distal parts. Of all the tested compounds, isoquercitrin was the most efficient CYP inducer, namely in the middle part of small intestine. Obtained data demonstrate the different effects of flavonoid glycosides and aglycone on CYP expression in rat liver and small intestine. Since these phytochemicals are xenobiotics, and thus they can increase the human risk of cancer development, their consumption in large quantities should be carefully considered.

Department of Biochemistry Faculty of Science Charles University Prague Hlavova 2030 128 40 Prague 2 Czech Republic

Zobrazit více v PubMed

Atkinson C, Frankenfeld CL, Lampe JW. Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med (Maywood) 2005;230:155–170. PubMed

Burke MD, Mayer RT. Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metab Dispos. 1974;2:583–588. PubMed

Canivenc-Lavier MC, Vernevaut MF, Totis M, Siess MH, Magdalou J, Suschetet M. Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver. Toxicology. 1996;114:19–27. PubMed

Ciolino HP, Daschner PJ, Yeh GC. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem J. 1999;340:715–722. PubMed PMC

Day AJ, DuPont MS, Ridley S, Rhodes M, Rhodes MJ, Morgan MR, Williamson G. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett. 1998;436:71–75. PubMed

Gee JM, DuPont MS, Rhodes MJ, Johnson IT. Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med. 1998;25:19–25. PubMed

Hodek P, Křížková J, Burdová K, Šulc M, Kizek R, Hudeček J, Stiborová M. Chemopreventive compounds – view from the other side. Chem Biol Interact. 2009;180:1–9. PubMed

Hodek P, Trefil P, Stiborová M. Flavonoids – potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact. 2002;139:1–21. PubMed

Jang EH, Park YC, Chung WG. Effects of dietary supplements on induction and inhibition of cytochrome P450s protein expression in rats. Food Chem Toxicol. 2004;42:1749–1756. PubMed

Křížková J, Burdová K, Hudeček J, Stiborová M, Hodek P. Induction of cytochromes P450 in small intestine by chemopreventive compounds. Neuro Endocrinol Lett. 2008;29:717–721. PubMed

Morris ME, Zhang S. Flavonoid-drug interactions: effects of flavonoids on ABC transporters. Life Sci. 2006;78:2116–2130. PubMed

Parkar SG, Stevenson DE, Skinner MA. The potential influence of fruit polyphenols on colonic microflora and human gut health. Int J Food Microbiol. 2008;124:295–298. PubMed

Ryu SD, Chung WG. Induction of the procarcinogen-activating CYP1A2 by a herbal dietary supplement in rats and humans. Food Chem Toxicol. 2003;41:861–866. PubMed

Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150:76–85. PubMed

Zhang L, Zuo Z, Lin G. Intestinal and hepatic glucuronidation of flavonoids. Mol Pharm. 2007;4:833–845. PubMed