title: Bioconcentration and metabolism of ketoconazole and effects on multi-biomarkers in crucian carp (Carassius auratus).
abstract: The tissue distribution, bioconcentration, metabolism and biological effects of the antifungal medication ketoconazole were investigated in fish, crucian carp (Carassius auratus) were exposed to a series of nominal concentrations (0.2, 2 and 20 μg/L) for 14 days. The ultra-high performance liquid chromatography tandem triple quadrupole mass spectroscopy (UPLC/MS/MS) analysis was used to determine the bioconcentration of ketoconazole and its metabolites in fish. The highest tissue concentration of ketoconazole was observed in the liver with the bioconcentration factor of 257.2, which is lower than the estimated BCF value. The ability of crucian carp to metabolize ketoconazole was confirmed and the results pointed out the existence of seven metabolites likely formed via oxidation of imidazole ring and the metabolic alteration of the piperazine rings. In addition, acetylcholinesterase, 7-ethoxyresorufin O-deethylase, superoxide dismutase and glutathione S-transferase changed significantly after 3, 7 and 14 days of exposure (P < 0.05), which indicated that the accumulation and metabolism of ketoconazole in fish tissues may account for the biological effects.
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China. Electronic address: ghlu@hhu.edu.cn.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Lu
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Haohan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
authors.forename: Peifang
authors.initials: P
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006054:Goldfish / Q000378:metabolism*; D007654:Ketoconazole / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D019363:Cytochrome P-450 CYP1A1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D000110:Acetylcholinesterase; D007654:Ketoconazole
keywords: Bioconcentration; Biomarker; Ketoconazole; Metabolism