Sobańska Anna W, Sobański Andrzej M
Department of Analytical Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland.
Molecules. 2024 Dec 11;29(24):5836. doi: 10.3390/molecules29245836.
One of the functions of placenta is to protect the fetus against harmful xenobiotics. Protective mechanisms of placenta are based on enzymes, e.g., antioxidant enzymes from the glutathione -transferases group (GST) or human N-acetyltransferase 2 (NAT2). Many organic sunscreens are known to cross biological barriers-they are detected in mother's milk, semen, umbilical cord blood or placental tissues. Some organic sunscreens are able to cross the placenta and to interfere with fetal development; they are known or suspected endocrine disruptors or neurotoxins. In this study, 16 organic sunscreens were investigated in the context of their placenta permeability and interactions with gluthatione S-transferase and human N-acetyltransferase 2 enzymes present in the human placenta. Binary permeability models based on discriminant analysis and artificial neural networks proved that the majority of studied compounds are likely to cross the placenta by passive diffusion. Molecular docking analysis suggested that some sunscreens show stronger affinity for glutathione S-transferase and human N-acetyltransferase 2 that native ligands (glutathione and Coenzyme A for GST and NAT2, respectively)-it is therefore possible that they are able to reduce the enzyme's protective activity. It was established that sunscreens bind to the studied enzymes mainly by alkyl, hydrogen bonds, van der Waals, π-π, π-alkyl and π-sulfur interactions. To conclude, sunscreens may become stressors affecting humans by different mechanisms and at different stages of development.
胎盘的功能之一是保护胎儿免受有害的外源性物质影响。胎盘的保护机制基于酶，例如谷胱甘肽转移酶组（GST）中的抗氧化酶或人类N - 乙酰转移酶2（NAT2）。许多有机防晒剂已知能够穿过生物屏障——它们在母乳、精液、脐带血或胎盘组织中被检测到。一些有机防晒剂能够穿过胎盘并干扰胎儿发育；它们是已知或疑似的内分泌干扰物或神经毒素。在本研究中，对16种有机防晒剂的胎盘通透性以及它们与人类胎盘中存在的谷胱甘肽S - 转移酶和人类N - 乙酰转移酶2的相互作用进行了研究。基于判别分析和人工神经网络的二元通透性模型证明，大多数研究化合物可能通过被动扩散穿过胎盘。分子对接分析表明，一些防晒剂对谷胱甘肽S - 转移酶和人类N - 乙酰转移酶2的亲和力比天然配体（分别为GST的谷胱甘肽和NAT2的辅酶A）更强——因此它们有可能降低酶的保护活性。已确定防晒剂与所研究的酶主要通过烷基、氢键、范德华力、π - π、π - 烷基和π - 硫相互作用结合。总之，防晒剂可能通过不同机制在人类发育的不同阶段成为影响人类的应激源。
