Co-treatment with indole-3-carbinol and resveratrol modify porcine CYP1A and CYP3A activities and expression.
1. Humans and animals are commonly exposed to indole-3-carbinol (I3C) and resveratrol (RES) via food or beverages. Moreover, these compounds have been demonstrated to potentially cause food-drug interactions. However, information about their combined effects is limited. Therefore, we investigated the effects of I3C and RES, both as single compounds and in combination, on cytochrome P450 1A and 3A activity and gene expression. 2. Using porcine microsomes, we demonstrated that RES caused non-competitive inhibition of CYP1A activity and un-competitive inhibition of CYP3A activity. Compared to the effect of single compounds, co-treatment with I3C and RES increased a degree of inhibition of CYP1A activity. 3. In porcine primary hepatocytes, treatment with I3C and RES resulted in induction of CYP1A1, CYP1A2 and CYP3A29 mRNA expression. 4. In conclusion, we demonstrated that both RES and I3C could cause food-drug interactions and that the combined effect could be more potent in doing so.
a Department of Molecular Sciences , Swedish University of Agricultural Sciences , Uppsala , Sweden.|b Faculty of Fisheries and Protection of Waters , South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, University of South Bohemia in Ceske Budejovice , Vodnany , Czech Republic.
Galia
G
Zamaratskaia
c Department of Food Science , Aarhus University , Tjele , Denmark.
Rebekka
R
Thøgersen
d Agricultural Institute of Slovenia , Ljubljana , Slovenia , and.|e Faculty of Agriculture and Life Sciences , University of Maribor , Hoče , Slovenia.
Marjeta
M
Čandek-Potokar
c Department of Food Science , Aarhus University , Tjele , Denmark.
Martin Krøyer
MK
Rasmussen
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology; D018565:Food-Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine
D065692:Cytochrome P-450 CYP3A Inhibitors; D007211:Indoles; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid; D013267:Stilbenes; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D000077185:Resveratrol
Detoxification; food–drug; gene-regulation; liver; secondary plant metabolites