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给怀孕母羊低剂量三氯生会导致胎盘摄取,并降低胎儿肝脏和胎盘的雌二醇硫酸转移酶活性。

Administration of low dose triclosan to pregnant ewes results in placental uptake and reduced estradiol sulfotransferase activity in fetal liver and placenta.

机构信息

Department of Medicinal Chemistry, University of Florida, Gainesville, FL, 32610, USA.

Department of Medicinal Chemistry, University of Florida, Gainesville, FL, 32610, USA.

出版信息

Toxicol Lett. 2018 Sep 15;294:116-121. doi: 10.1016/j.toxlet.2018.05.014. Epub 2018 May 26.

Abstract

Sulfonation is a major pathway of estrogen biotransformation with a role in regulating estrogen homeostasis in humans and sheep. Previous in vitro studies found that triclosan is an especially potent competitive inhibitor of ovine placental estrogen sulfotransferase, with K of <0.1 nM. As the placenta is the main organ responsible for estrogen synthesis in pregnancy in both women and sheep, and the liver is another site of estrogen biotransformation, this study examined the effects of triclosan exposure of pregnant ewes on placental and hepatic sulfotransferase activity. Triclosan, 0.1 mg/kg/day, or saline vehicle was administered to late gestation fetal sheep for two days either by direct infusion into the fetal circulation or infusion into the maternal blood. On the third day, fetal liver and placenta were harvested and analyzed for triclosan and for cytosolic estradiol sulfotransferase activity. Placenta contained higher concentrations of triclosan than liver in each individual sheep in both treatment groups. There was a negative correlation between triclosan tissue concentration (pmol/g tissue) and cytosolic sulfotransferase activity (pmol/min/mg protein) towards estradiol. These findings demonstrated that in the sheep exposed to very low concentrations of triclosan, this substance is taken up into placenta and reduces estrogen sulfonation.

摘要

磺化作用是雌激素生物转化的主要途径,在调节人和绵羊的雌激素内稳态中起作用。先前的体外研究发现,三氯生是绵羊胎盘雌激素磺基转移酶的一种特别有效的竞争性抑制剂,其 K 值<0.1 nM。由于胎盘是女性和绵羊妊娠期间雌激素合成的主要器官,而肝脏是雌激素生物转化的另一个部位,因此本研究检测了三氯生暴露于妊娠绵羊对胎盘和肝磺基转移酶活性的影响。三氯生,0.1 mg/kg/天,或生理盐水载体通过直接输注到胎儿循环或输注到母体血液中,连续两天给予妊娠晚期胎儿绵羊。第三天,收获胎儿肝脏和胎盘,并分析三氯生和细胞溶质雌二醇磺基转移酶活性。在两个治疗组中,每个绵羊的胎盘组织中的三氯生浓度都高于肝脏。三氯生组织浓度(pmol/g 组织)与细胞溶质磺基转移酶对雌二醇的活性(pmol/min/mg 蛋白)呈负相关。这些发现表明,在暴露于极低浓度三氯生的绵羊中,该物质被摄取到胎盘并减少雌激素磺化。

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