New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases
文献类型：期刊论文
| 作者 | Liu, Xin2; Cao, Yun-Feng1; Ran, Rui-Xue3; Dong, Pei-Pei5; Gonzalez, Frank J.9; Wu, Xue6,7,8; Huang, Ting1; Chen, Jian-Xin1; Fu, Zhi-Wei6,7,8; Li, Rong-Shan3 |
| 刊名 | CHEMOSPHERE
 |
| 出版日期 | 2016-02-01 |
| 卷号 | 144页码:1966-1972 |
| 关键词 | Phthalates Udp-glucuronosyltransferases (Ugts) Di-n-octyl Ortho-phthalate (Dnop) Diphenyl Phthalate (Dphp) |
| ISSN号 | 0045-6535 |
| DOI | 10.1016/j.chemosphere.2015.10.076 |
| 文献子类 | Article |
| 英文摘要 | Wide utilization of phthalates-containing products results in the significant exposure of humans to these compounds. Many adverse effects of phthalates have been documented in rodent models, but their effects in humans exposed to these chemicals remain unclear until more mechanistic studies on phthalate toxicities can be carried out. To provide new insights to predict the potential adverse effects of phthalates in humans, the recent study investigated the inhibition of representative phthalates di-n-octyl ortho-phthalate (DNOP) and diphenyl phthalate (DPhP) towards the important xenobiotic and endobiotic-metabolizing UDP-glucuronosyltransferases (UGTs). An in vitro UGTs incubation system was employed to study the inhibition of DNOP and DPhP towards UGT isoforms. DPhP and DNOP weakly inhibited the activities of UGT1A1, UGT1A7, and UGT1A8. 100 mu M of DNOP inhibited the activities of UGT1A3, UGT1A9, and UGT2B7 by 41.8% (p < 0.01), 45.6% (p < 0.01), and 48.8% (p < 0.01), respectively. 100 mu M of DPhP inhibited the activity of UGT1A3, UGT1A6, and UGT1A9 by 81.8 (p < 0.001), 49.1% (p < 0.05), and 76.4% (p < 0.001), respectively. In silica analysis was used to explain the stronger inhibition of DPhP than DNOP t9wards UGT1A3 activity. Kinetics studies were carried our to determine mechanism of inhibition of UGT1A3 by DPhP. Both Dixon and Lineweaver-Burk plots showed the competitive inhibition of DPhP towards UGT1A3. The inhibition kinetic parameter (KO was calculated to be 0.89 mu M. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1>[I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), these studies predicted in vivo drug-drug interaction might occur when the plasma concentration of DPhP was above 0.089 mu M. Taken together, this study reveales the potential for adverse effects of phthalates DNOP and DPhP as a result of UGT inhibition. (C) 2015 Elsevier Ltd. All rights reserved. |
| WOS关键词 | METABOLIZING ENZYME ; RECEPTOR ; ESTERS ; MILK ; GENE ; RAT |
| WOS研究方向 | Environmental Sciences & Ecology |
| 语种 | 英语 |
| WOS记录号 | WOS:000367774400249 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/171478]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Fang, Zhong-Ze |
| 作者单位 | 1.Shanghai Inst Planned Parenthood Res, Key Lab Contracept & Devices Res NPFPC, Shanghai Engn & Technol Res Ctr Reprod Hlth Drug, Shanghai, Peoples R China 2.Liaoning Med Univ, Affiliated Hosp 1, Jinzhou, Liaoning, Peoples R China 3.Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China 4.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin 300070, Peoples R China 5.Dalian Med Univ, Inst Integrat Med, Dalian, Peoples R China 6.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China 7.Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China 8.Dalian Univ, Affiliated Zhongshan Hosp, Dalian 116012, Peoples R China 9.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA |
| 推荐引用方式 GB/T 7714 | Liu, Xin,Cao, Yun-Feng,Ran, Rui-Xue,et al. New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases[J]. CHEMOSPHERE,2016,144:1966-1972. |
| APA | Liu, Xin.,Cao, Yun-Feng.,Ran, Rui-Xue.,Dong, Pei-Pei.,Gonzalez, Frank J..,...&Fang, Zhong-Ze.(2016).New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases.CHEMOSPHERE,144,1966-1972. |
| MLA | Liu, Xin,et al."New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases".CHEMOSPHERE 144(2016):1966-1972. |
入库方式： OAI收割
来源：大连化学物理研究所
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