title: Dried chicory root modifies the activity and expression of porcine hepatic CYP3A but not 2C--effect of in vitro and in vivo exposure.
abstract: Hepatic cytochrome P450 expression and activity are dependent on many factors, including dietary ingredients. In the present study, we investigated the in vivo and in vitro effect of chicory root on hepatic CYP3A and 2C in male pigs. Chicory feeding increased the expression of CYP3A29 mRNA but not CYP2C33. Correspondingly, CYP3A activity was increased by chicory feeding, while CYP2C activity was not affected. Additionally, the in vitro effect of chicory extract on the CYP3A activity was investigated. It was shown that CYP3A activity in the microsomes from male pigs was inhibited, but this effect was eliminated by pre-incubation. In both male and female pigs the CYP3A activity was increased in the presence of chicory after pre-incubation. Furthermore, gender-related differences in mRNA expression and activity were observed. CYP3A mRNA expression was greater in female pigs; this was not reflected on activity. For CYP2C, no difference in mRNA expression was observed, while CYP2C activity was greater in female pigs. Surprisingly, the expression of the constitutive androstane receptor, pregnane X receptor and aryl hydrocarbon receptor did not differ with feed or gender. In conclusion, chicory root modifies the expression and activity of CYP3A in vivo and in vitro, while CYP2C is not affected.
authors.affiliation: Department of Food Science, Aarhus University, Denmark. Martink.rasmussen@agrsci.dk
authors.forename: Martin Krøyer
authors.initials: MK
authors.lastname: Rasmussen
authors.forename: Galia
authors.initials: G
authors.lastname: Zamaratskaia
authors.forename: Bente
authors.initials: B
authors.lastname: Andersen
authors.forename: Bo
authors.initials: B
authors.lastname: Ekstrand
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed / Q000009:adverse effects*; D000818:Animals; D018651:Cichorium intybus; D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D000090702:Constitutive Androstane Receptor; D010936:Plant Extracts; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A