Liu Jianchao, Lu Guanghua, Yang Haohan, Yan Zhenhua, Wang Yonghua, Wang Peifang
Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
Key Laboratory for Integrated Regulation and Resources Development on Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, PR China.
Chemosphere. 2016 May;150:145-151. doi: 10.1016/j.chemosphere.2016.02.033. Epub 2016 Feb 19.
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.
研究了抗真菌药物酮康唑在鱼类中的组织分布、生物富集、代谢及生物学效应，将鲫鱼（Carassius auratus）暴露于一系列标称浓度（0.2、2和20μg/L）的酮康唑中14天。采用超高效液相色谱串联三重四极杆质谱（UPLC/MS/MS）分析法测定鱼类中酮康唑及其代谢物的生物富集情况。在肝脏中观察到酮康唑的最高组织浓度，生物富集系数为257.2，低于估计的BCF值。证实了鲫鱼代谢酮康唑的能力，结果指出可能存在七种通过咪唑环氧化和哌嗪环代谢改变形成的代谢物。此外，暴露3、7和14天后，乙酰胆碱酯酶、7-乙氧基异吩恶唑酮O-脱乙基酶、超氧化物歧化酶和谷胱甘肽S-转移酶发生了显著变化（P<0.05），这表明酮康唑在鱼组织中的积累和代谢可能是其生物学效应的原因。
