title: Impact of Fusarium mycotoxins on hepatic and intestinal mRNA expression of cytochrome P450 enzymes and drug transporters, and on the pharmacokinetics of oral enrofloxacin in broiler chickens.
abstract: Cytochrome P450 (CYP450) drug biotransformation enzymes and multidrug resistance (MDR) proteins may influence drug disposition processes. The first part of the study aimed to evaluate the effect of mycotoxins deoxynivalenol (DON) and/or fumonisins (FBs), at contamination levels approaching European Union guidance levels, on intestinal and hepatic CYP450 enzymes and MDR proteins gene expression in broiler chickens. mRNA expression of genes encoding CYP450 enzymes (CYP3A37, CYP1A4 and CYP1A5) and drug transporters (MDR1/ABCB1 and MRP2/ABCC2) was determined using qRT-PCR. A significant up-regulation of CYP1A4 (P = 0.037) and MDR1 (P = 0.036) was observed in the jejunum of chickens fed a diet contaminated with FBs. The second part of this study aimed to investigate the impact of feeding a FBs contaminated diet on the oral absorption of enrofloxacin (10 mg/kg BW), a MDR1 substrate. A significant (P = 0.045), however small, decreased area under the plasma concentration-time curve (AUC0-48h, mean ± SD) was observed for enrofloxacin in chickens fed the FBs contaminated diet compared to the control group, 16.28 ± 1.82 h μg/mL versus 18.27 ± 1.79 h μg/mL. These findings suggest that concurrent administration of drugs with FBs contaminated feed might alter the pharmacokinetic characteristics of CYP1A4 substrate drugs and MDR1 substrates, such as enrofloxacin.
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium; Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Gunther.Antonissen@UGent.be.
authors.forename: Gunther
authors.initials: G
authors.lastname: Antonissen
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Mathias.Devreese@UGent.be.
authors.forename: Mathias
authors.initials: M
authors.lastname: Devreese
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Siegrid.DeBaere@UGent.be.
authors.forename: Siegrid
authors.initials: S
authors.lastname: De Baere
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: An.Martel@UGent.be.
authors.forename: An
authors.initials: A
authors.lastname: Martel
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Filip.VanImmerseel@UGent.be.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Immerseel
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Siska.Croubels@UGent.be.
authors.forename: Siska
authors.initials: S
authors.lastname: Croubels
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002645:Chickens; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D005506:Food Contamination / Q000032:analysis; D005670:Fusarium / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014018:Tissue Distribution
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D009183:Mycotoxins; D012333:RNA, Messenger; D000077422:Enrofloxacin; D003577:Cytochrome P-450 Enzyme System
keywords: Broiler chicken; Cytochrome P450; Drug transporters; Enrofloxacin; Fumonisins; Mycotoxins