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 (Journal article)

Mannerstrom, M./ Zorn-Kruppa, M./ Diehl, H./ Engelke, M./ Toimela, T./ Maenpaa, H./ Huhtala, A./ Uusitalo, H./ Salminen, L./ Pappas, P./ Marselos, M./ Mantyla, M./ Mantyla, E./ Tahti, H.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: retinal pigment epithelial cultures,drug effects,cell proliferation,breast-cancer cells,ocular toxicity,aminoglycoside antibiotics,tamoxifen,5-fluorouracil,chloroquine,toremifene,gentamicin,pharmacokinetics,retinopathy
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/21799
ISSN: 0887-2333
Link: <Go to ISI>://000174917300012
http://ac.els-cdn.com/S0887233301001138/1-s2.0-S0887233301001138-main.pdf?_tid=cdce270948e330ce5cef6d72206859bd&acdnat=1333004324_5040b6891b4198d13ffd3dba6e4fd436
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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