PMID- 27490210 OWN - NLM STAT- MEDLINE DCOM- 20170213 LR - 20181202 IS - 1872-7077 (Electronic) IS - 1382-6689 (Linking) VI - 46 DP - 2016 Sep TI - Effects of inducers of cytochrome P450s on enrofloxacin N-deethylation in crucian carp Carassius auratus gibelio. PG - 188-193 LID - S1382-6689(16)30193-4 [pii] LID - 10.1016/j.etap.2016.07.015 [doi] AB - 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) (12mg/kg) and beta-naphthoflavone (BNF) (12mg/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 CmaxCF/CmaxEF ratio was 4.41, 0.81 and 0.95, and the corresponding value of the AUC0-t-CF/AUC0-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 30.88h, and the corresponding values for CF were 5.79, 35.18 and 38.11h, 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Fu, Guihong AU - Fu G AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. FAU - Zhou, Chang AU - Zhou C AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. FAU - Wang, Yuan AU - Wang Y AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. FAU - Fang, Wenhong AU - Fang W AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. Electronic address: fwenhong@163.com. FAU - Zhou, Junfang AU - Zhou J AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. FAU - Zhao, Shu AU - Zhao S AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. FAU - Ma, Licai AU - Ma L AD - East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of East China Sea and Oceanic Fishery Resources Exploitation and Utilization, Ministry of Agriculture, 300 Jungong Road, Shanghai, 200090, China. LA - eng PT - Journal Article DEP - 20160726 PL - Netherlands TA - Environ Toxicol Pharmacol JT - Environmental toxicology and pharmacology JID - 9612020 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cytochrome P-450 Enzyme Inducers) RN - 0 (Fluoroquinolones) RN - 3DX3XEK1BN (Enrofloxacin) RN - 6051-87-2 (beta-Naphthoflavone) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - VJT6J7R4TR (Rifampin) SB - IM MH - Animals MH - Anti-Bacterial Agents/blood/*pharmacokinetics MH - Cytochrome P-450 CYP1A1/metabolism MH - Cytochrome P-450 CYP3A/metabolism MH - Cytochrome P-450 Enzyme Inducers/*pharmacology MH - Drug Interactions MH - Enrofloxacin MH - Fluoroquinolones/blood/*pharmacokinetics MH - Goldfish/blood/*metabolism MH - Microsomes, Liver/drug effects/*enzymology MH - Rifampin/pharmacology MH - beta-Naphthoflavone/pharmacology OTO - NOTNLM OT - Ciprofloxacin OT - Cytochrome P450s OT - Enrofloxacin OT - N-Deethylation EDAT- 2016/08/05 06:00 MHDA- 2017/02/14 06:00 CRDT- 2016/08/05 06:00 PHST- 2016/04/08 00:00 [received] PHST- 2016/07/18 00:00 [revised] PHST- 2016/07/23 00:00 [accepted] PHST- 2016/08/05 06:00 [entrez] PHST- 2016/08/05 06:00 [pubmed] PHST- 2017/02/14 06:00 [medline] AID - S1382-6689(16)30193-4 [pii] AID - 10.1016/j.etap.2016.07.015 [doi] PST - ppublish SO - Environ Toxicol Pharmacol. 2016 Sep;46:188-193. doi: 10.1016/j.etap.2016.07.015. Epub 2016 Jul 26.