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双酚 S 作为潜在胎儿暴露的替代物,其安全性是否优于双酚 A?灌流人胎盘的胎盘转运。

Is bisphenol S a safer alternative to bisphenol A in terms of potential fetal exposure ? Placental transfer across the perfused human placenta.

机构信息

INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France.

INTHERES, Université de Toulouse, INRA, ENVT, 31 076 Toulouse, France.

出版信息

Chemosphere. 2019 Apr;221:471-478. doi: 10.1016/j.chemosphere.2019.01.065. Epub 2019 Jan 10.

Abstract

The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 μM) and non-labelled BPSG (2.5 μM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 μM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure.

摘要

我们的研究目的是使用灌流人胎盘模型评估双酚 S(BPS)及其主要代谢物 BPS 葡萄糖醛酸(BPSG)的双向传递,并将获得的值与双酚 A(BPA)和 BPA 葡萄糖醛酸进行比较。14 个足月胎盘在开放的双回路中进行灌流,回路中含有氘标记的 BPS(1 和 5 μM)和非标记的 BPSG(2.5 μM)以及自由扩散标记物安替比林(800 ng/ml),同时存在白蛋白(25 mg/ml)。在第二个实验中,使用已建立的 P-糖蛋白抑制剂 PSC833(2 和 4 μM)研究了 P-糖蛋白在 BPS 主动跨胎盘屏障外排中的潜在作用。BPS 在两个方向上的胎盘转移均低于 BPA。BPS 在母胎方向的胎盘清除指数比相反方向低三倍,强烈表明存在一些主动外排转运。然而,我们的结果表明 P-糖蛋白并不参与限制 BPS 的母胎转移。BPSG 在胎儿隔室中的胎盘转移几乎不存在,表明在胎儿隔室中,BPSG 主要来源于胎-胎盘代谢。BPSG 的胎儿-母体清除指数比母体-胎儿指数高 20 倍。我们得出结论,与 BPA 相比,血-胎盘屏障更有效地限制了胎儿对 BPS 的暴露,这表明胎盘在保护人类胎儿免受 BPS 暴露方面发挥着至关重要的作用。

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