Development of an in vitro blood–brain barrier model to study the effects of endosulfan on the permeability of tight junctions and a comparative study of the cytotoxic effects of endosulfan on rat and human glial and neuronal cell cultures
Development of an in vitro blood–brain barrier model to study the effects of endosulfan on the permeability of tight junctions and a comparative study of the cytotoxic effects of endosulfan on rat and human glial and neuronal cell cultures
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DOI：
10.1002/tox.20175
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发表时间：
2006-06
影响因子：
4.5
通讯作者：
M. Chan;S. Morisawa;Aki Nakayama;Y. Kawamoto;M. Yoneda
中科院分区：
文献类型：
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作者：
M. Chan;S. Morisawa;Aki Nakayama;Y. Kawamoto;M. Yoneda
硫丹是一种环二烯类有机氯杀虫剂，是控制蔬菜、棉花和水果害虫最常用的杀虫剂之一。利用猪脑微血管内皮细胞建立模型，研究硫丹对血脑屏障（BBB）紧密连接通透性的影响。当用α硫丹、β硫丹或硫丹硫酸盐处理时，血脑屏障渗透性（以跨内皮电阻测量）以剂量和时间依赖性方式降低。细胞毒性测试表明，三种硫丹在浓度为10 μM及以下时不会导致细胞死亡。暴露于0.01-10 μM浓度后，从外室到内室的过滤器培养的内皮细胞单层对14 C-硫丹（Pe）的平均渗透率与从内室到外室的平均渗透率之比约为1：1.2-2.1。α硫丹、β硫丹和硫丹硫酸盐对大鼠神经胶质细胞（C6）和神经元细胞（PC 12）培养物以及人类神经胶质细胞（CCF-STTG 1）和神经元细胞（NT 2）培养物具有细胞毒性作用。α-硫丹的影响具有高度选择性，在不同的培养物中发现的LC 50值范围很广，从CCF‐ STTG 1细胞的11.2 μM到PC 12细胞的48.0 μM不等。相比之下，暴露于硫丹硫酸盐后，神经胶质和神经元细胞培养物中的选择性神经毒性并不那么明显，因为LC 50值在10.4-21.6 μM范围内。CCF‐ STTG 1细胞对α硫丹和硫丹硫酸盐更敏感，而NT 2细胞对β硫丹更敏感。© 2006 Wiley Periodicals，Inc.环境毒理学21：223-235，2006年。
Endosulfan, an organochlorine (OC) insecticide that belongs to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton, and fruits. Porcine brain microvascular endothelial cells were used to develop a model to study the effects of endosulfan on the permeability of tight junctions in the blood–brain barrier (BBB). BBB permeability, measured as transendothelial electrical resistance, decreased in a dose‐ and time‐dependent manner when treated with α‐endosulfan, β‐endosulfan, or endosulfan sulfate. Cytotoxicity testing revealed that the three endosulfans did not cause cell death at concentrations of 10 μM and below. The ratio of the average permeability of the filter‐grown endothelial cell monolayer to 14C‐endosulfan (Pe) going from the outer to the inner compartments with that going from the inner to the outer compartments was approximately 1:1.2–2.1 after exposure to concentrations of 0.01–10 μM. α‐Endosulfan, β‐endosulfan, and endosulfan sulfate had cytotoxic effects on rat glial (C6) and neuronal (PC12) cell cultures as well as on human glial (CCF‐STTG1) and neuronal (NT2) cell cultures. The effects of α‐endosulfan were highly selective, with a wide range of LC50 values found in the different cultures, ranging from 11.2 μM for CCF‐STTG1 cells to 48.0 μM for PC12 cells. In contrast, selective neurotoxicity was not so manifest in glial and neuronal cell cultures after exposure to endosulfan sulfate, as LC50 values were in the range of 10.4–21.6 μM. CCF‐STTG1 cells were more sensitive to α‐endosulfan and endosulfan sulfate, whereas NT2 cells were more sensitive to β‐endosulfan. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 223–235, 2006.