Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Res Vet Sci. 2011 Feb;90(1):99-105. doi: 10.1016/j.rvsc.2010.04.025. Epub 2010 May 23.
The inhibitory effects of fluoroquinolones on the enzyme activity, protein levels and mRNA expression of liver cytochrome P450 (CYP) 1A and 3A were investigated in male broiler chicks. Enrofloxacin (20 mg/kg), sarafloxacin (8 mg/kg) and marbofloxacin (5.5 mg/kg) were administrated in drinking water for 7 consecutive days. A cocktail of the probe drugs caffeine and dapsone was used to determine CYP1A and 3A activity. Western blot analysis and real-time PCR were used to determine the effects on protein levels of CYP1A and 3A, and on CYP1A4, 1A5, 3A37 mRNA levels. Enrofloxacin increased the half-life of elimination for both caffeine and dapsone, and decreased expression of CYP1A and 3A protein. Marbofloxacin decreased the metabolism of caffeine and expression of CYP1A protein. However, no change in mRNA expression was observed for any treatment group. This suggested that high doses of enrofloxacin and marbofloxacin, but not sarafloxacin, inhibit CYP in chick liver raising the possibility of drug-drug interaction when using these compounds.
本研究旨在探讨氟喹诺酮类药物对雄性肉鸡肝脏细胞色素 P450（CYP）1A 和 3A 酶活性、蛋白水平和 mRNA 表达的抑制作用。将恩诺沙星（20mg/kg）、沙拉沙星（8mg/kg）和马波沙星（5.5mg/kg）添加至饮水中，连续给药 7 天。采用探针药物组合（咖啡因和氨苯砜）来测定 CYP1A 和 3A 的活性，采用 Western blot 分析和实时 PCR 来测定 CYP1A 和 3A 蛋白水平以及 CYP1A4、1A5、3A37 mRNA 水平的变化。结果表明，恩诺沙星增加了咖啡因和氨苯砜的消除半衰期，并降低了 CYP1A 和 3A 蛋白的表达。马波沙星降低了咖啡因的代谢和 CYP1A 蛋白的表达，但各处理组的 mRNA 表达均未发生变化。这表明高剂量的恩诺沙星和马波沙星而非沙拉沙星可抑制鸡肝脏中的 CYP，提示在使用这些化合物时可能会发生药物相互作用。
