School of Pharmacy/Toxicology, Faculty of Health Sciences, University of Eastern Finland, Finland.
Farenta Oy (a part of Oriola), Orionintie 5, Espoo, Finland.
Toxicol Lett. 2020 Jun 15;326:70-77. doi: 10.1016/j.toxlet.2020.02.014. Epub 2020 Feb 27.
In addition to the transfer across the placenta, placenta displays hormonal and xenobiotic metabolism, as well as enzymatic defense against oxidative stress. We analyzed aromatase (CYP19A1), uridine 5'-diphospho-glucuronyltransferase (UGT), glutathione-S-transferase (GST) and catalase (CAT) activities in over 70 placentas from nonsmokers stored at -80 °C from former perfusion studies. A wide interindividual variation in all activities was found. Longterm storage at -80 °C did not affect the activities. Ethoxyresorufin-O-deethylase (EROD, CYP1A1) was not detected in any of the studied placentas perfused with chemicals. Several compounds in placental perfusion changed statistically significantly the enzyme activities in placental tissue. Melamine and nicotine increased CYP19A1, melamine increased UGT and GST, PhIP with ethanol decreased CYP19A1 and increased GST, and PhIP with buprenorphine decreased CAT. Antipyrine in 100 μg/ml also changed the studied enzyme activities, but not statistically significantly. Because antipyrine is a reference compound in placental perfusions, its potential effects must be taken into account in human placental perfusion. Enzyme activities deserve further studies as biomarkers of placental toxicity. Finally, enzyme activities deserve further studies as biomarkers of placental toxicity.
除了胎盘的转运作用外，胎盘还具有激素和外源性代谢物代谢、以及抗氧化应激的酶防御作用。我们分析了来自 70 多个非吸烟人群的胎盘，这些胎盘来自于以前的灌注研究，在-80°C 下储存。发现所有活性的个体间差异很大。长期在-80°C 下储存不会影响活性。在任何用化学物质灌注的研究胎盘组织中都未检测到乙氧基试卤灵-O-脱乙基酶（EROD，CYP1A1）。胎盘灌注中的几种化合物统计学上显著改变了胎盘组织中的酶活性。三聚氰胺和尼古丁增加了 CYP19A1，三聚氰胺增加了 UGT 和 GST，与乙醇的 PhIP 降低了 CYP19A1 并增加了 GST，与丁丙诺啡的 PhIP 降低了 CAT。100μg/ml 的安替比林也改变了研究中的酶活性，但没有统计学意义。由于安替比林是胎盘灌注中的参考化合物，因此在人体胎盘灌注中必须考虑其潜在影响。酶活性值得进一步研究，作为胎盘毒性的生物标志物。最后，酶活性值得进一步研究，作为胎盘毒性的生物标志物。
