Evaluation of the cytotoxicity of selected systemic and intravitreally dosed drugs in the cultures of human retinal pigment epithelial cell line and of pig primary retinal pigment epithelial cells
Evaluation of the cytotoxicity of selected systemic and intravitreally dosed drugs in the cultures of human retinal pigment epithelial cell line and of pig primary retinal pigment epithelial cells
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DOI：
10.1016/s0887-2333(01)00113-8
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发表时间：
2002-04-01
影响因子：
3.2
通讯作者：
Tähti, H
中科院分区：
文献类型：
--
作者：
Mannerström, M;Zorn-Kruppa, M;Tähti, H
体外研究了他莫昔芬、托瑞米芬、氯喹、5-氟尿嘧啶、庆大霉素和更昔洛韦对视网膜色素上皮（RPE）的细胞毒性。采用WST-1试验对人RPE细胞系D407和猪RPE细胞培养进行细胞毒性测定，WST-1试验是细胞增殖和活力的测定，实验条件对WST-1试验细胞密度的影响。测定培养基中血清含量、暴露时间。他莫昔芬处理的D407细胞的EC50值在6.7 - 8.9 μ mol/l之间，猪RPE细胞的EC50值在10.1 - 12.2 μ mol/l之间，这取决于所使用的细胞密度。托瑞米芬在D407细胞中的对应值为7.4 ~ 11.1 μ mol/l，在猪RPE细胞中的对应值为10.0 ~ 11.6 μ mol/l。在氯喹处理的细胞中，D407细胞的EC50值为110.0 μ mol/l，猪RPE细胞的EC50值为58.4 μ mol/l。庆大霉素和更昔洛韦在微摩尔浓度下没有引起任何毒性。暴露时间是一个重要因素，特别是当药物不诱导细胞死亡，但具有抗增殖作用时（5-氟尿嘧啶）。血清保护细胞免受药物的毒性作用，两种细胞培养对他莫昔芬和托瑞米芬最敏感，其次是氯喹。在本研究中获得的药物毒性在两种细胞类型中非常相似。即猪RPE细胞和人d407细胞系，尽管在生长速度和黑色素含量等细胞类型方面存在差异。由于RPE对整个神经视网膜具有重要的内稳态功能，因此RPE是评估视网膜毒性的一个有趣的体外模型，但是，除了WST-1测试外，还需要基于RPE内稳态功能的更具体的测试和标记。(C) 2002年Elsevier Science Ltd.出版
The cytotoxicity of the selected systemic and intravitreally dosed drugs tamoxifen, toremifene, chloroquine, 5-fluorouracil, gentamicin and ganciclovir was studied in retinal pigment epithelium (RPE) in vitro. The cytotoxicity was assayed in the human RPE cell line D407 and the pig RPE cell culture using the WST-1 test, which is an assay of cell proliferation and viability, The effects of experimental conditions on the WST-1 test (cell density. serum content in the culture medium, the exposure time) were evaluated. The EC50 Values in tamoxifen-treated D407 cells ranged between 6.7 and 8.9 mumol/l, and in pig RPE cells between 10.1 and 12.2 mumol/l, depending on the cell density used. The corresponding values for toremifene were 7.4 to 11.1 mumol/l in D407 cells and 10.0 to 11.6 mumol/l in pig RPE cells. In chloroquine-treated cells, the EC50 values were 110.0 mumol/l for D407 cells and 58.4 mumol/l for pig RPE cells. Gentamicin and ganciclovir did not shock any toxicity in micromolar concentrations. The exposure time was a significant factor, especially when the drug did not induce cell death, but was antiproliferative (5-fluorouracil). Serum protected the cells from the toxic effects or the drugs, Both cell cultures were most sensitive to tamoxifen and toremifene, and next to chloroquine. The drug toxicities obtained in the present study were quite similar in both cell tyupes. that is, the pig RPE cells and the human D 407 cell line, despite the differences in, for example, the growth rate and melanin contents Of the cell types. Owing to the homeostatic functions important for the whole neuroretina, RPE is an interesting in vitro model for the evaluation of retinal toxicity, but, in addition to the WST-1 test, more specific tests and markers based on the homeostatic functions of the RPE are needed. (C) 2002 Published by Elsevier Science Ltd.