Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro
Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro
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DOI：
10.1016/j.neulet.2008.01.071
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发表时间：
2008-04
影响因子：
2.5
通讯作者：
Hui-wen Yang;Hai-yan Liu;Xiang Liu;Dong-Mei Zhang;Yu-chun Liu;Xiao-dong Liu;Guang-Ji Wang;Lin Xie
中科院分区：
文献类型：
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作者：
Hui-wen Yang;Hai-yan Liu;Xiang Liu;Dong-Mei Zhang;Yu-chun Liu;Xiao-dong Liu;Guang-Ji Wang;Lin Xie
为探讨苯巴比妥(PB)、苯妥英钠(PHT)、卡马西平(CBZ)和丙戊酸(VPA)4种典型抗癫痫药物(AEDs)长期作用对原代培养的大鼠脑微血管内皮细胞(RBMECs)P-糖蛋白(P-gp)水平和功能的影响。年龄匹配的细胞在正常培养液中孵育。药物作用60天后，分别用罗丹明123(Rho123)积累法和Western印迹法检测细胞P-gp功能和水平。药物处理的细胞中Rho123的积聚低于年龄匹配的细胞。环孢素A(CsA)和维拉帕米(Ver)可增加药物处理细胞和年龄匹配细胞中Rho123的积聚。药物处理细胞中Rho123积聚增加的幅度大于年龄匹配细胞。在药物处理的细胞中，较高的P-gp水平与Rho123积聚的减少一致。结果证实了长期暴露于四种抗癫痫药物可诱导rBMECs P-gp功能和水平的假说。
To investigate whether long-term exposure to four typical antiepileptic drugs (AEDs): phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and valproic acid (VPA) can increase P-glycoprotein (P-gp) level and function in primary cultured rat brain microvascular endothelial cells (rBMECs) in vitro, the rBMECs were incubated in culture medium containing indicated drugs (PB, PHT, CBZ, VPA and rifampin) for 60 days in a gradient concentration manner. Age-matched cells were incubated in normal culture medium. After a 60-day exposure to the indicated drugs, P-gp function and level in cells were measured using rhodamine 123 (Rho123) accumulations and Western blot analysis, respectively. Lower Rho123 accumulation in drug-treated cells was found than that in age-matched cells. Cyclosporin A (CsA) and verapamil (Ver) increased Rho123 accumulation both in drug-treated cells and age-matched cells. The magnitude of increased Rho123 accumulation in drug-treated cells was larger than that in age-matched cells. Higher P-gp levels were found to be consistent with decrease of Rho123 accumulation in drug-treated cells. The results verified the hypothesis that long-term exposure to the four antiepileptic drugs can induce P-gp function and level in rBMECs.