title: Improvac does not modify the expression and activities of the major drug metabolizing enzymes cytochrome P450 3A and 2C in pigs.
abstract: In the present study, we investigated hepatic mRNA expression and activities of CYP3A and 2C in entire, surgically castrated and pigs vaccinated with Improvac. Additionally, we examined the mRNA expression of the two nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR), known to regulate CYP3A and 2C mRNA expression, respectively. Activities of CYP3A and 2C were estimated as a rate of 7-benzyloxy-4-trifluoromethylcoumarin and 7-benzyloxyquinoline metabolism (CYP3A) and tolbutamide metabolism (CYP2C). We found no effect of Improvac treatment or surgical castration on either CYP3A or 2C activities. Similarly, the mRNA expressions of CYP3A29, 2C33 and PXR were not changed. CAR mRNA expression differed only between entire and surgically castrated male pigs (p=0.005), being greater in surgically castrated pigs. Our results indicated that neither CYP3A nor 2C are affected by Improvac.
authors.affiliation: University of Veterinary and Pharmaceutical Science Brno, Faculty of Hygiene and Ecology, Department of Meat Hygiene and Technology, Brno, Czech Republic. tomankova.janicka@seznam.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Tomankova
authors.forename: Martin Krøyer
authors.initials: MK
authors.lastname: Rasmussen
authors.forename: Kristina
authors.initials: K
authors.lastname: Andersson
authors.forename: Bo
authors.initials: B
authors.lastname: Ekstrand
authors.forename: Galia
authors.initials: G
authors.lastname: Zamaratskaia
mesh_terms: D000818:Animals; D002369:Castration / Q000009:adverse effects; D000090702:Constitutive Androstane Receptor; D003374:Coumarins / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008297:Male; D000077297:Pregnane X Receptor; D011804:Quinolines / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis; D013552:Swine; D014044:Tolbutamide / Q000378:metabolism; D022642:Vaccines, Contraceptive / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: C419147:7-benzyloxy-4-trifluoromethylcoumarin; D000090702:Constitutive Androstane Receptor; D003374:Coumarins; D000077297:Pregnane X Receptor; D011804:Quinolines; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D022642:Vaccines, Contraceptive; C400322:cytochrome P-450 CYP2C subfamily; C065956:7-benzyloxyquinoline; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D051544:Cytochrome P-450 CYP3A