Toxic effects of dietary exposure to T-2 toxin on intestinal and hepatic biotransformation enzymes and drug transporter systems in broiler chickens

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 68 μg/kg or 752 μg/kg T-2 toxin. After 3 weeks, 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 752 μg/kg T-2. For CYP1A4, even a contamination level of 68 μg/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 752 μg/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 752 μg/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.

► Broiler chickens were exposed to 68 or 752 μg T-2/kg feed for 3 weeks. ► A reduced BW gain was observed when feeding 752 μg T-2/kg feed. ► 752 μg T-2/kg feed led to downregulation of hepatic CYP1A4, CYP1A5, CYP3A37, MRP2. ► 752 μg T-2/kg feed led to higher CYP3A activity in ileum and liver. ► Both biotransformation enzymes and drug transporter systems are influenced by T-2.