title: Toxic effects of dietary exposure to T-2 toxin on intestinal and hepatic biotransformation enzymes and drug transporter systems in broiler chickens.
abstract: The effects of the mycotoxin T-2 on hepatic and intestinal drug-metabolizing enzymes (cytochrome P450) and drug transporter systems (MDR1 and MRP2) in poultry were investigated during this study. Broiler chickens received either uncontaminated feed, feed contaminated with 68μg/kg or 752μg/kg T-2 toxin. After 3weeks, the animals were euthanized and MDR1, MRP2, CYP1A4, CYP1A5 and CYP3A37 mRNA expression were analyzed using qRT-PCR. Along the entire length of the small intestine no significant differences were observed. In the liver, genes coding for CYP1A4, CYP1A5 and CYP3A37 were significantly down-regulated in the group exposed to 752μg/kg T-2. For CYP1A4, even a contamination level of 68μg/kg T-2 caused a significant decrease in mRNA expression. Expression of MDR1 was not significantly decreased in the liver. In contrast, hepatic MRP2 expression was significantly down-regulated after exposure to 752μg/kg T-2. Hepatic and intestinal microsomes were prepared to test the enzymatic activity of CYP3A. In the ileum and liver CYP3A activity was significantly increased in the group receiving 752μg/kg T-2 compared to the control group. The results of this study show that drug metabolizing enzymes and drug transporter mechanisms can be influenced due to prolonged exposure to relevant doses of T-2.
authors: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Belgium. ann.osselaere@ugent.be
authors: A
authors: A
authors: Osselaere
authors: S J
authors: SJ
authors: Li
authors: L
authors: L
authors: De Bock
authors: M
authors: M
authors: Devreese
authors: J
authors: J
authors: Goossens
authors: V
authors: V
authors: Vandenbroucke
authors: J
authors: J
authors: Van Bocxlaer
authors: K
authors: K
authors: Boussery
authors: F
authors: F
authors: Pasmans
authors: A
authors: A
authors: Martel
authors: P
authors: P
authors: De Backer
authors: S
authors: S
authors: Croubels
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D002645:Chickens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D017931:DNA Primers; D004032:Diet; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013605:T-2 Toxin / Q000633:toxicity*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003577:Cytochrome P-450 Enzyme System; D017931:DNA Primers; D013605:T-2 Toxin; D000097202:ATP-Binding Cassette Sub-Family B Member 4