In vitro metabolic kinetics of cresyl diphenyl phosphate (CDP) in liver microsomes of crucian carp (Carassius carassius).
In vitro metabolic kinetics of cresyl diphenyl phosphate (CDP) in liver microsomes of crucian carp (Carassius carassius).
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DOI：
10.1016/j.envpol.2021.116586
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发表时间：
2021-01
影响因子：
8.9
通讯作者：
Zhenfei Yan;C. Feng;Xiaowei Jin;Daqing Liu;Yajun Hong;Yu Qiao;Yingchen Bai;Hyo-Bang Moon;A. Qadeer;Fengchang Wu
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文献类型：
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作者：
Zhenfei Yan;C. Feng;Xiaowei Jin;Daqing Liu;Yajun Hong;Yu Qiao;Yingchen Bai;Hyo-Bang Moon;A. Qadeer;Fengchang Wu
磷酸甲苯基二苯酯（CDP）是一种芳基取代的有机磷酸酯（OPEs），是一种常见的阻燃剂和增塑剂。由于CDP在生物体内的积累，因此研究CDP的毒理机制和代谢过程具有重要意义。因此，制备鲫鱼肝微粒体，进行体外代谢动力学试验，以估算胞苷二磷酸的代谢率。孵育140 min后，CDP的消耗占给药浓度的58.1%-77.1%（0.5和2 μM除外）。消耗速率最符合Michaelis-Menten模型（R2= 0.995），其中最大速度（Vmax）和Michaelis-Menten常数（Km）分别为12，700 ± 2120 pmol min−1·mg− 1蛋白质和1030 ± 212 μM。CDP的体外肝清除率（克林特）为12.3 μL min-1·mg-1 protein。芳基OPEs的对数值Kowand生物富集系数（BCF）均高于烷基和氯代OPEs，表明CDP在水生生物中易积累。结果表明，CDP在肝微粒体中的代谢速率大于以往研究中检测到的其他OPEs。本文首次全面研究了CDP在鱼肝微粒体中的体外代谢动力学。本研究为了解这类物质的环境归趋和代谢过程提供了有用的信息，也为新兴污染物的生态风险评价提供了理论依据。
Cresyl diphenyl phosphate (CDP), as a kind of aryl substituted organophosphate esters (OPEs), is commonly used as emerging flame retardants and plasticizers detected in environmental media. Due to the accumulation of CDP in organisms, it is very important to discover the toxicological mechanism and metabolic process of CDP. Hence, liver microsomes of crucian carps (Carassius carassius) were prepared forin vitrometabolism kinetics assay to estimate metabolism rates of CDP. After 140 min incubation, the depletion of CDP accounted for 58.1%–77.1% (expect 0.5 and 2 μM) of the administrated concentrations. The depletion rates were best fitted to the Michaelis-Menten model (R2= 0.995), where maximum velocity (Vmax) and Michaelis-Menten constant (Km) were 12,700 ± 2120 pmol min−1·mg−1protein and 1030 ± 212 μM, respectively. Moreover, thein vitrohepatic clearance (CLint) of CDP was 12.3 μL min−1·mg−1protein. Log Kowand bioconcentration factor (BCF) of aryl-OPEs were both higher than those of alkyl- and chlorinated-OPEs, indicating that CDP may easily accumulate in aquatic organisms. The results made clear that the metabolism rate of CDP was greater than those of other OPEs detected in liver microsomes in previous research. This paper was first of its kind to comprehensively investigate thein vitrometabolic kinetics of CDP in fish liver microsomes. The present study might provide useful information to understand the environmental fate and metabolic processes of these kinds of substances, and also provide a theoretical basis for the ecological risk assessment of emerging contaminants.