1. Administration of low dose triclosan to pregnant ewes results in placental uptake and reduced estradiol sulfotransferase activity in fetal liver and placenta.
- Author
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Jackson EN, Rowland-Faux L, James MO, and Wood CE
- Subjects
- Animals, Anti-Infective Agents, Local administration & dosage, Anti-Infective Agents, Local metabolism, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors metabolism, Estradiol metabolism, Female, Fetus blood supply, Fetus drug effects, Fetus metabolism, Infusions, Intravenous, Liver embryology, Liver metabolism, Placenta enzymology, Placenta metabolism, Pregnancy, Sheep, Domestic, Sulfotransferases metabolism, Tissue Distribution, Toxicokinetics, Triclosan administration & dosage, Triclosan metabolism, Anti-Infective Agents, Local toxicity, Enzyme Inhibitors toxicity, Liver drug effects, Maternal Exposure adverse effects, Placenta drug effects, Sulfotransferases antagonists & inhibitors, Triclosan toxicity
- 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
ic 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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