1. Co-treatment with indole-3-carbinol and resveratrol modify porcine CYP1A and CYP3A activities and expression
- Author
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Galia Zamaratskaia, Marjeta Čandek-Potokar, Rebekka Thøgersen, and Martin Krøyer Rasmussen
- Subjects
0301 basic medicine ,Male ,Receptors, Steroid ,Indoles ,CYP3A ,Swine ,Health, Toxicology and Mutagenesis ,Cytochrome P-450 CYP3A Inhibitors/pharmacology ,Resveratrol ,Pharmacology ,Toxicology ,Biochemistry ,ENTIRE MALE PIGS ,HEPATOCYTES ,chemistry.chemical_compound ,food–drug ,Food-Drug Interactions ,0302 clinical medicine ,Stilbenes ,Indole-3-carbinol ,Receptors, Steroid/genetics ,Cytochrome P-450 CYP3A ,MESSENGER-RNA EXPRESSION ,DIETARY INDOLE-3-CARBINOL ,DRUG-INTERACTION ,Regulation of gene expression ,biology ,Indoles/pharmacology ,Pregnane X Receptor ,General Medicine ,Cytochrome P-450 CYP3A/genetics ,030220 oncology & carcinogenesis ,RED WINE ,Microsomes, Liver ,Detoxification ,Hepatocytes/drug effects ,food-drug ,Cytochrome P-450 CYP1A1/antagonists & inhibitors ,ARYL-HYDROCARBON RECEPTOR ,Gene Expression Regulation, Enzymologic/drug effects ,METABOLISM ,liver ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,gene-regulation ,Cytochrome P-450 CYP1A1 ,Animals ,SKATOLE ,secondary plant metabolites ,Messenger RNA ,CYP1A2 ,Cytochrome P450 ,CYTOCHROME-P450 ,Receptors, Aryl Hydrocarbon/genetics ,030104 developmental biology ,chemistry ,Receptors, Aryl Hydrocarbon ,Stilbenes/pharmacology ,biology.protein ,Microsome ,Hepatocytes ,Microsomes, Liver/drug effects ,Cytochrome P-450 CYP3A Inhibitors - Abstract
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.
- Published
- 2017
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