| Literature DB >> 28753904 |
Yun-Feng Cao1, Zuo Du2, Zhi-Tu Zhu3, Hong-Zhi Sun3, Zhi-Wei Fu4, Kun Yang2, Yong-Zhe Liu2, Cui-Min Hu5, Pei-Pei Dong6, Frank J Gonzalez7, Zhong-Ze Fang8.
Abstract
Phthalate esters (PAEs) have been extensively used in industry as plasticizers and there remains concerns about their safety. The present study aimed to determine the inhibition of phthalate esters (PAEs) on the activity of the phase II drug-metabolizing enzymes UDP-glucuronosyltransferases (UGTs). In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone was used to investigate the inhibition potentials of PAEs towards various s UGTs. PAEs exhibited no significant inhibition of UGT1A1, UGT1A3, UGT1A8, UGT1A10, UGT2B15, and UGT2B17, and limited inhibition of UGT1A6, UGT1A7 and UGT2B4. However, UGT1A9 was strongly inhibited by PAEs. In silico docking demonstrated a significant contribution of hydrogen bonds and hydrophobic interactions contributing to the inhibition of UGT by PAEs. The Ki values were 15.5, 52.3, 23.6, 12.2, 5.61, 2.79, 1.07, 22.8, 0.84, 73.7, 4.51, 1.74, 0.58, 6.79, 4.93, 6.73, and 7.23 μM for BBOP-UGT1A6, BBZP-UGT1A6, BBOP-UGT1A7, BBZP-UGT1A7, DiPP-UGT1A9, DiBP-UGT1A9, DCHP-UGT1A9, DBP-UGT1A9, BBZP-UGT1A9, BBOP-UGT1A9, DMEP-UGT1A9, DPP-UGT1A9, DHP-UGT1A9, DiBP-UGT2B4, DBP-UGT2B4, DAP-UGT2B4, and BBZP-UGT2B4, respectively. In conclusion, exposure to PAEs might influence the metabolic elimination of endogenous compounds and xenobiotics through inhibiting UGTs.Entities:
Keywords: Kinetic parameters; Phthalate esters; Uridine diphosphate glucuronosyltransferases
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Year: 2017 PMID： 28753904 PMCID： PMC6331009 DOI： 10.1016/j.chemosphere.2017.07.105
Source DB: PubMed Journal: Chemosphere ISSN： 0045-6535 Impact factor: 7.086