New insights for the risk of bisphenol A: inhibition of UDP-glucuronosyltransferases (UGTs).
Bisphenol A (BPA), the important endocrine-disrupting chemical (EDC), has been reported to be able to induce various toxicity. The present study aims to understand the toxicity behavior of bisphenol A through evaluating the inhibition profile of bisphenol A towards UDP-glucuronosyltransferase (UGT) isoforms. In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as probe reaction for all the tested UGT isoforms. The results showed that bisphenol A exerted stronger inhibition towards UGT2B isoforms than UGT1A isoforms. Furthermore, the inhibition kinetic type and parameters (K(i)) were determined for the inhibition of bisphenol A towards UGT2B4, 2B7, 2B15, and 2B17. Bisphenol A exhibited the competitive inhibition towards UGT2B4, and noncompetitive inhibition towards UGT2B7, 2B15 and 2B17. The inhibition kinetic parameters (K(i)) were calculated to be 1.1, 32.6, 5.6, and 19.9 μM for UGT2B4, 2B7, 2B15 and 2B17, respectively. In combination with the in vivo concentration of bisphenol A, the elevation of exposure dose was predicted to increase by 29.1%, 1%, 5.7%, and 1.6% for UGT2B4, 2B7, 2B15, and 2B17, indicating the high influence of bisphenol A towards the in vivo UGT2B isofroms-mediated metabolism of xenobiotics and endogenous substances. All these data provide the supporting information for deeper understanding of toxicology of bisphenol A.
Liaoning Medical University, Jinzhou, Liaoning, China. Electronic address: lyyyjhm@163.com.
Hua-Mao
HM
Jiang
Zhong-Ze
ZZ
Fang
Yun-Feng
YF
Cao
Cui-Min
CM
Hu
Xiao-Yu
XY
Sun
Mo
M
Hong
Ling
L
Yang
Guang-Bo
GB
Ge
Yong
Y
Liu
Yan-Yan
YY
Zhang
Qiang
Q
Dong
Ren-Jie
RJ
Liu
D001559:Benzhydryl Compounds / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D018570:Risk Assessment; D015262:Xenobiotics / Q000633:toxicity*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004791:Enzyme Inhibitors; D014453:Glucuronosyltransferase; D010636:Phenols; D015262:Xenobiotics; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Bisphenol A; Recombinant enzymes; Risk evaluation; UDP-glucuronosyltransferase (UGT)