羟基化多溴联苯醚(OH-PBDEs)在小鼠肝脏S9中的体外代谢研究

羟基化多溴联苯醚(OH-PBDEs)是一类具有内分泌干扰性质的酚类化合物,且内分泌干扰效应大于其母体多溴联苯醚(PBDEs),研究OH-PBDEs的体外代谢行为对于理解其在生物体内的富集转化具有重要意义.以小鼠肝脏S9部分作为研究对象,考察了3-OH-BDE-47、5-OHBDE-47、6-OH-BDE-47和2'-OH-BDE-68在小鼠肝脏中的体外代谢.结果表明小鼠肝脏S9中的I相酶和II相酶均能代谢4种OH-PBDEs;醚键与OH官能团及Br原子互为邻位时,I相酶对OH-PBDEs的代谢率最高,即6-OH-BDE-47表现出较高的代谢率,此外,4种OH-PBDEs经I相酶代谢后均能生成2,4-二溴苯酚,表明醚键断裂是其主要的I相酶代谢途径;OH-PBDEs的OH官能团与醚键互为间位时,II相酶对其葡萄糖醛酸结合反应最高,也就是5-OH-BDE-47表现出较高的去除率.     

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.