Co-treatment with indole-3-carbinol and resveratrol modify porcine CYP1A and CYP3A activities and expression

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.

Keywords:

• Detoxification
• food–drug
• gene-regulation
• liver
• secondary plant metabolites

Acknowledgements

The financial support from the Lundbeck Foundation to M.K.R is greatly acknowledged. M.Č.P was financed by Slovenian Research Agency (grants P4-0133 and L4-5521). This work was also supported by Swedish University of Agricultural Sciences, NL faculty.

Declaration of interest

All authors declare that there are no conflicts of interest in this study.

Supplementary material available online