Environmental Pollution ( IF 7.6 ) Pub Date : 2018-10-12 , DOI: 10.1016/j.envpol.2018.10.045 Anna Marqueño , Elisabet Pérez-Albaladejo , Cintia Flores , Encarnación Moyano , Cinta Porte
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BADGE (bisphenol A diglycidyl ether) is a synthesis product of bisphenol A (BPA), which, like other plasticizers, can cross the human placenta and reach the foetus. However, compared to BPA, there is almost no toxicological information. This work investigates the toxicity, endocrine and lipid disruption potential of BADGE and its hydrolysed and chlorinated derivatives (BADGE·H2O and BADGE·2HCl) in human placental JEG-3 cells. The analysis of culture medium by HPLC-ESI(+)-QqQ evidenced a good bioavailability of BADGE·2HCl and BADGE·H2O, but low stability of BADGE. Regardless, BADGE·2HCl and BADGE showed higher cytotoxicity than BADGE·H2O, which was the only compound that significantly inhibited CYP19 activity (IC50 49 ± 5 μM). JEG-3 cells lipidome analyzed by FIA-ESI(+/−)-Orbitrap was significantly altered by exposure to BADGE·2HCl and BADGE at concentrations at the low μM range. BADGE·2HCl lead to a strong decrease of diacyl- and triacyl-glycerides (DGs,TGs) together with some membrane lipids, while BADGE lead to an accumulation of TGs. The results evidence the ability of BADGE and derivatives to affect placental lipid handling and to modulate placental CYP19 activity (BADGE·H2O) and highlights the need to monitor human exposure to these compounds, at least as intensely as BPA is monitored.
中文翻译:
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双酚A二缩水甘油醚及其衍生物对人胎盘细胞的毒性作用
BADGE(双酚A二缩水甘油醚)是双酚A(BPA)的合成产物,与其他增塑剂一样,它可以穿过人类胎盘并到达胎儿。但是,与BPA相比,几乎没有毒理学信息。这项工作研究了BADGE及其水解和氯化衍生物(BADGE·H 2 O和BADGE·2HCl)在人胎盘JEG-3细胞中的毒性,内分泌和脂质破坏潜能。HPLC-ESI(+)-QqQ对培养基的分析表明,BADGE·2HCl和BADGE·H 2 O具有良好的生物利用度,但BADGE的稳定性较低。无论如何,BADGE·2HCl和BADGE的细胞毒性都比BADGE·H 2 O高,BADGE·H 2 O是唯一能显着抑制CYP19活性的化合物(IC 5049±5μM)。通过FIA-ESI(+/-)-Orbitrap分析的JEG-3细胞脂质组通过在低μM范围内暴露于BADGE·2HCl和BADGE而显着改变。BADGE·2HCl导致二酰基和三酰基甘油酯(DGs,TGs)以及某些膜脂质的大量减少,而BADGE导致TGs的积累。结果证明了BADGE及其衍生物影响胎盘脂质处理和调节胎盘CYP19活性(BADGE·H 2 O)的能力,并强调需要监测人体对这些化合物的暴露,至少与监测BPA一样强烈。