中文摘要：细胞色素P450（CYP450）药物生物转化酶和多药耐药（MDR）蛋白质会影响药物处置的过程。本研究第一部分旨在评估霉菌毒素脱氧雪腐镰刀菌烯醇（DON）和/或伏马菌素（FBs），在接近欧盟指导水平的污染水平，对肉鸡的肠和肝CYP450酶和MDR蛋白基因表达的作用。研究表明同时饲喂药物和FBs污染的饲料会改变CYP1A4及MDR1的底物药物，如恩诺沙星的药代动力学特征。
外文摘要：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 (AUC0-48 h, 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.
外文关键词：Broiler chicken；Cytochrome P450；Drug transporters；Enrofloxacin；Fumonisins；Mycotoxins
作者：Antonissen, G；Devreese, M；De Baere, S；Martel, A；Van Immerseel, F；Croubels, S
作者单位：Univ Ghent
期刊名称：FOOD AND CHEMICAL TOXICOLOGY
期刊影响因子：3.584
出版年份：2017
出版刊次：3
点击下载：镰刀菌毒素对肉鸡肝和肠细胞色素P450酶和药物转运蛋白的mRNA表达及对口服恩诺沙星的药代动力学的影响