OBJECTIVES: Since flavonoids and other natural compounds exert beneficial effects on human health, their consumption rapidly increases. However, they can modulate the activity of xenobiotic-metabolizing enzymes involved in activation and detoxification of food and environmental carcinogens. Thus, their potential negative effects should be examined. METHODS: The induction effects of selected chemopreventive compounds, administered per orally by gastric gavages to rats, on cytochrome P450 (CYP) 1A and 2B were determined in liver and small intestine using Western blotting analysis and specific metabolic activity assays. RESULTS: Comparing CYPs expression along small intestine, the highest induction was observed in the proximal part near pylorus with rapid decrease towards the distal part. In response to chemopreventive compounds, the marked induction of CYP1A and CYP2B in liver was observed after diallyl sulphide and flavone treatment. In small intestine, beta-naphthoflavone, diallyl sulphide and curcumin induced CYP1A1 and CYP2B1. In both tissues, resveratrol did not significantly affect CYPs expression. The results of Western blotting detection of CYPs correlate well with their specific enzymatic activities. CONCLUSIONS: Presented data indicate ambiguous impact of chemopreventive compounds on cytochromes P450, main xenobiotic-metabolizing enzymes. Thus, the question of safety and unlimited consumption of these compounds arises.

• MeSH
• alylové sloučeniny farmakologie   MeSH
• antikarcinogenní látky farmakologie   MeSH
• beta-naftoflavon farmakologie   MeSH
• cytochrom P-450 CYP1A1 biosyntéza   genetika   MeSH
• cytochrom P-450 CYP2B1 biosyntéza   genetika   MeSH
• flavonoidy farmakologie   MeSH
• játra enzymologie   účinky léků   MeSH
• krysa rodu rattus MeSH
• kurkumin farmakologie   MeSH
• potkani Wistar MeSH
• stilbeny farmakologie   MeSH
• sulfidy farmakologie   MeSH
• systém (enzymů) cytochromů P-450 biosyntéza   MeSH
• tenké střevo enzymologie   MeSH
• western blotting MeSH
• xenobiotika metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVES: Dihydromyricetin (DHM) is a flavonoid, which has been shown to antagonize effects of ethanol intoxication. As a potential pharmacological agent, its biological interactions with enzymes metabolizing foreign compounds should be tested. Thus, the aim of this study was to analyze the influence of DHM on the induction and metabolic activity of selected cytochromes P450 (CYPs). METHODS: After flavonoid administration by oral gavage to stomach the CYP expression at protein and mRNA levels was determined in rat liver and small intestine. The effects of flavonoids on CYP1A1/2, CYP1A2 or CYP2B1/2 enzyme activities in microsomes were measured using marker activities of these enzymes. Flavonoid-mediated inhibition of recombinant CYP1A2 was also assayed with luciferin-ME substrate. The flavonoid interaction with aryl hydrocarbon receptor (AhR) was assayed by reporter luciferase activity in Hep2G cells. RESULTS: The value of half maximal inhibitory concentration of DHM for CYP1A1/2, CYP1A2, and CYP2B1 were determined to be 4.1, 14.2, and 98.5 mmol.L(-1), respectively. With the exception of a weak induction of CYP2B1 and CYP1A2 in the middle part of small intestine and in the liver, respectively, DHM did not affect the CYP expression at protein levels. On the contrary, real-time PCR revealed elevated expression of CYP1A1 and CYP1A2 mRNA in proximal part of the small intestine while decreased in the middle part. In the study utilizing the HepG2 cells, DHM showed only an additive effect on the benzo[a]pyrene-mediated activation of Ah receptor. CONCLUSIONS: Dihydromyricetin doesn't significantly interfere with metabolic activity of CYP1A1/2 and CYP2B1 enzymes.

• MeSH
• flavonoly farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• játra účinky léků   enzymologie   MeSH
• karcinogeny metabolismus   MeSH
• krysa rodu rattus MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• messenger RNA účinky léků   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Wistar MeSH
• systém (enzymů) cytochromů P-450 účinky léků   genetika   metabolismus   MeSH
• tenké střevo účinky léků   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH