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Effects of inducers of cytochrome P450s on enrofloxacin N-deethylation in crucian carp Carassius auratus gibelio

文献类型： 外文期刊

作者： Fu, Guihong 1 ; Zhou, Chang 1 ; Wang, Yuan 1 ; Fang, Wenhong 1 ; Zhou, Junfang 1 ; Zhao, Shu 1 ; Ma, Licai 1 ;

作者机构： 1.Chinese Acad Fishery Sci, East China Sea Fisheries Res Inst, Key Lab East China Sea & Ocean Fishery Resources, Minist Agr, 300 Jungong Rd, Shanghai 200090, Peoples R China

关键词： Cytochrome P450s; N-Deethylation; Enrofloxacin; Ciprofloxacin

期刊名称：ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY （ 影响因子：4.86； 五年影响因子：4.462 ）

ISSN： 1382-6689

年卷期： 2016 年 46 卷

页码：

收录情况： SCI

摘要： In this study with crucian carp (Carassius auratus gibelio), the effect on enrofloxacin (EF) and its metabolite ciprofloxacin (CF) and on the activity of cytochrome P450 1A (CYP1A) and cytochrome P450 3A (CYP3A) was estimated following the oral administration of rifampicin (RIF) (12 mg/kg) and beta-naphthoflavone (BNF) (12 mg/kg), respectively. First, reversed-phase high-performance liquid chromatography (RP-HPLC) was used to detect the pharmacokinetics of EF with continual blood sampling. In RIF-treated, BNF-treated and control groups, the value of the C-maxCF/C-maxEF ratio was 4.41, 0.81 and 0.95, and the corresponding value of the AUC(0-t-CF)/AUC(0-t-EF) ratio was 3.69, 1.84 and 1.76, respectively. In the RIF-treated, BNF-treated and control groups, the MRT values of EF were 26.57, 27.45 and 30.88 h, and the corresponding values for CF were 5.79, 35.18 and 38.11 h, respectively. Based on these results for crucian carp, the accumulation and elimination of EF and CF in the RIF-treated group were more rapid than in BNF-treated and control groups. Second, liver microsomes were pretreated with the inducer of CYP1A for BNF and that of CYP3A for RIF, and then the enzymatic activities of CYP1A and CYP3A were measured, respectively. The activities of ethoxyresorufin-O-deethylation (EROD) and erythromycin-N-demethylation (ERND) increased significantly (P<0.05) for CYP1A and CYP3A, respectively. However, in further experiments on the formation of CF, the level of EF N-deethylation was significantly induced by RIF and inhibited by ketoconazole (KTZ) for CYP3A but had no influence for CYP1A, BNF and berberine chloride (BER). We concluded that CYP3A might be responsible for the N-deethylation of EF and because of this activity, could also serve as a toxicity biomarker in crucian carp. (C) 2016 Elsevier B.V. All rights reserved.

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