Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes
Rao, Kaifeng; Hou, Rui; Wang, Zijian; Xu, Yiping; Huang, Chao
刊名ENVIRONMENTAL SCIENCE & TECHNOLOGY
2018-03-06
卷号52期号:5页码:3202-3210
ISSN号0013-936X
文献子类Article
英文摘要Tris(2-butoxyethyl) phosphate (TBOEP) and tris(n-butyl) phosphate (TNBP) are the most commonly used alkyl organophosphate esters (alkyl-OPEs), and they increasingly accumulate in organisms and create potential health hazards. This study examined the metabolism of TNBP and TBOEP in Carassius carassius liver and intestinal microsomes and the production of their corresponding monohydroxylated and dealkylated metabolites. After 140 min of incubation with fish liver microsomes, the rapid depletion of TNBP and TBOEP were both best fitted to the Michaelis-Menten model (at administrated concentrations ranging from 0.5 to 200 mu M), with a CLint (intrinsic clearance) of 3.1 and 3.9 mu L.min(-1).mg(-1) protein, respectively. But no significant (P > 0.05) biotransformation was observed for these compounds in intestinal microsomes at any administrated concentrations. In fish liver assay, bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) and bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3-OH-TBOEP) were the most abundant metabolites of TBOEP, and dibutyl-3-hydroxybutyl phosphate (3-OH-TNBP) was the predominant metabolite of TNBP. Similarly, the apparent V-max values (maximum metabolic rate) of BBOEHEP and 3-OH-TNBP were also respectively highest among those of other metabolites. Further inhibition studies were conducted to identify the specific cytochrome P450 (CYP450) isozymes involved in the metabolism of TNBP and TBOEP in liver microsomes. It was confirmed that CYP3A4 and CYP1A were the significant CYP450 isoforms catalyzing the metabolism of TNBP and TBOEP in fish liver microsomes. Overall, this study emphasized the importance of hydroxylated metabolites as biomarkers for alkyl-OPEs exposure, and further research is needed to validate the in vivo formation and toxicological implications of these metabolites.
内容类型期刊论文
源URL[http://ir.rcees.ac.cn/handle/311016/41329]  
专题生态环境研究中心_中国科学院饮用水科学与技术重点实验室
推荐引用方式
GB/T 7714
Rao, Kaifeng,Hou, Rui,Wang, Zijian,et al. Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2018,52(5):3202-3210.
APA Rao, Kaifeng,Hou, Rui,Wang, Zijian,Xu, Yiping,&Huang, Chao.(2018).Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes.ENVIRONMENTAL SCIENCE & TECHNOLOGY,52(5),3202-3210.
MLA Rao, Kaifeng,et al."Characterized in Vitro Metabolism Kinetics of Alkyl Organophosphate Esters in Fish Liver and Intestinal Microsomes".ENVIRONMENTAL SCIENCE & TECHNOLOGY 52.5(2018):3202-3210.
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