Flavonoids are abundant polyphenols in nature. They are extensively biotransformed in enterocytes and hepatocytes, where conjugated (methyl, sulfate, and glucuronide) metabolites are formed. However, bacterial microflora in the human intestines also metabolize flavonoids, resulting in the production of smaller phenolic fragments (e.g., hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes). Despite the fact that several colonic metabolites appear in the circulation at high concentrations, we have only limited information regarding their pharmacodynamic effects and pharmacokinetic interactions. Therefore, in this in vitro study, we investigated the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes. Our results demonstrated that some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin. However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin; nevertheless, only its effect on CYP2C9 seems to be relevant. Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. Our results demonstrate that, besides flavonoid aglycones and their conjugated derivatives, some colonic metabolites are also able to interact with proteins involved in the pharmacokinetics of drugs.

• Klíčová slova
• CYP450 enzymes, O-desmethylangolensin, colonic flavonoid metabolites, pharmacokinetic interaction, phloroglucinol, polyphenols, resorcinol, serum albumin,
• MeSH
• erytrocyty enzymologie   MeSH
• flavonoidy * chemie   metabolismus   MeSH
• hepatocyty enzymologie   MeSH
• lidé MeSH
• lidský sérový albumin * chemie   metabolismus   MeSH
• systém (enzymů) cytochromů P-450 * chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• flavonoidy * MeSH
• lidský sérový albumin * MeSH
• systém (enzymů) cytochromů P-450 * MeSH

Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in human beings. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about the regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors. Finally, we reflect on the need for further research, to clarify the interaction between active feed components and the porcine CYP system.

• Klíčová slova
• bioactive compounds, phase I enzymes, pig, skatole,
• MeSH
• biotransformace MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P450 CYP2A6 genetika   metabolismus   MeSH
• krmivo pro zvířata * MeSH
• lidé MeSH
• pohlavní steroidní hormony metabolismus   MeSH
• prasata metabolismus   MeSH
• sekvenční homologie MeSH
• skatol metabolismus   MeSH
• xenobiotika metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytochrom P-450 CYP2E1 MeSH
• cytochrom P450 CYP2A6 MeSH
• pohlavní steroidní hormony MeSH
• skatol MeSH
• xenobiotika MeSH

The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin with Ki values from 1.7 to 2.6 μM. BROD activity was inhibited by quercetin with Ki values from 64.9 to 75.3 μM and naringenin with Ki values from 39.3 to 45.8 μM. The IC50 and Ki values did not differ between the groups of mice with different levels of POPs exposure in any of the experimental sets. Sesamin did not inhibit either EROD or BROD. We concluded that the interactions of quercetin and naringenin with CYP1A and CYP3A in mice liver were not affected by the levels of POPs exposure.

• MeSH
• cytochrom P-450 CYP3A MeSH
• dioxoly farmakologie   MeSH
• flavanony farmakologie   MeSH
• jaterní mikrozomy enzymologie   patologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lignany farmakologie   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• myši MeSH
• quercetin farmakologie   MeSH
• rodina 1 cytochromu P450 metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   enzymologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CYP3A protein, mouse MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• dioxoly MeSH
• flavanony MeSH
• látky znečišťující vzduch MeSH
• lignany MeSH
• naringenin MeSH Prohlížeč
• quercetin MeSH
• rodina 1 cytochromu P450 MeSH
• sesamin MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH