Discovery of a widespread metabolic pathway within and among phenolic   xenobiotics

doi:10.1073/pnas.1700558114

CORC > 北京大学 > 城市与环境学院

	Discovery of a widespread metabolic pathway within and among phenolic xenobiotics
	Ashrap, Pahriya ; Zheng, Guomao ; Wan, Yi ; Li, Tong ; Hu, Wenxin ; Li, Wenjuan ; Zhang, Hong ; Zhang, Zhaobin ; Hu, Jianying
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2017
关键词	triclosan phenolic xenobiotic liver microsome metabolic kinetics cross-talk reaction CONSTITUTIVE ANDROSTANE RECEPTOR REGULATING TRICLOSAN UNITED-STATES BISPHENOL-A METHYL TRICLOSAN CYTOCHROMES P450 ENZYMES LIVER TRICLOCARBAN INDUCTION
DOI	10.1073/pnas.1700558114
英文摘要	Metabolism is an organism's primary defense against xenobiotics, yet it also increases the production of toxic metabolites. It is generally recognized that phenolic xenobiotics, a group of ubiquitous endocrine disruptors, undergo rapid phase II metabolism to generate more water-soluble glucuronide and sulfate conjugates as a detoxification pathway. However, the toxicological effects of the compounds invariably point to the phase I metabolic cytochrome P450 enzymes. Here we show that phenolic xenobiotics undergo an unknown metabolic pathway to form more lipophilic and bioactive products. In a nontargeted screening of the metabolites of a widely used antibacterial ingredient: triclosan (TCS), we identified a metabolic pathway via in vitro incubation with weever, quail, and human microsomes and in vivo exposure in mice, which generated a group of products: TCS-O-TCS. The lipophilic metabolite of TCS was frequently detected in urine samples from the general population, and TCS-O-TCS activated the constitutive androstane receptor with the binding activity about 7.2 times higher than that of the parent compound. The metabolic pathway was mediated mainly by phase I enzymes localized on the microsomes and widely observed in chlorinated phenols, phenols, and hydroxylated aromatics. The pathway was also present in different phenolic xenobiotics and formed groups of unknown pollutants in organisms (e.g., TCS-O-bisphenol A and TCS-O-benzo(a)pyrene), thus providing a cross-talk reaction between different phenolic pollutants during metabolic processes in organisms.; National Natural Science Foundation of China [21422701, 201677003, 41330637]; National Basic Research Program of China [2015CB458900]; Undergraduate Student Research Training Program; 111 Project at Peking University [B14001]; SCI(E); ARTICLE; 23; 6062-6067; 114
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/472893]
专题	城市与环境学院
推荐引用方式 GB/T 7714	Ashrap, Pahriya,Zheng, Guomao,Wan, Yi,et al. Discovery of a widespread metabolic pathway within and among phenolic xenobiotics[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2017.
APA	Ashrap, Pahriya.,Zheng, Guomao.,Wan, Yi.,Li, Tong.,Hu, Wenxin.,...&Hu, Jianying.(2017).Discovery of a widespread metabolic pathway within and among phenolic xenobiotics.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.
MLA	Ashrap, Pahriya,et al."Discovery of a widespread metabolic pathway within and among phenolic xenobiotics".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017).