Cytotoxic effect of ciprofloxacin in primary culture of rat astrocytes and protection by Vitamin E

被引:38
|
作者
Gurbay, Aylin [1 ]
Gonthier, Brigitte
Barret, Luc
Favier, Alain
Hincal, Filiz
机构
[1] Hacettepe Univ, Fac Pharm, Dept Toxicol, TR-06100 Ankara, Turkey
[2] Hacettepe Univ, Fac Pharm, Dept Pharmaceut Technol, TR-06100 Ankara, Turkey
[3] CEA, Fac Med Grenoble, UMR E UJF, ORSOX,Lab Oligoelements & Resistance Stress Oxyda, La Tronche, France
[4] CEA, Dept Rech Fondamentale Matiere Condensee, Serv Chim Inorgan & Biol, Lab Lesions Acides Nucle, Grenoble, France
关键词
ciprofloxacin; central nervous system; Astrocytes; cytotoxicity; oxidative stress; hormesis;
D O I
10.1016/j.tox.2006.09.016
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to investigate the possible cytotoxic and oxidative stress inducing effects of ciprofloxacin (CPFX) on primary cultures of rat astrocytes. The cultured cells were incubated with various concentrations of CPFX (0.5-300 mg/l), and cytotoxicity was determined by neutral red (NR) and MTT assays. Survival profile of cells was biphasic in NR assay: CPFX did not cause any alteration at any concentration for 7 h, whereas <= 50 mg/l concentrations induced significant cell proliferation in incubation periods of 24, 48, 72, and 96 h. However, cell proliferation gradually decreased at higher concentrations, and 200 and 300 mg/l of CPFX exposure was found to be significantly (p < 0.05) cytotoxic at all time periods. With MTT assay, no alteration was noted for incubation period of 7 h, as observed with NR assay. But, cell viability decreased with similar to >= 50 mg/l CPFX exposure in all other time periods. Cell proliferation was only seen in 24 h of incubation with 0.5 and 5 mg/l CPFX. Vitamin E pretreatment of cell cultures were found to be providing complete protection against cytotoxicity of 300 mg/1 CPFX in 96 h incubation when measured with both NR and MTT assays. The SOD pretreatment was partially protective with NR assay, but no protection was noted when measured with MTT. A significant enhancement of lipid peroxidation was observed with the cytotoxic concentration of the drug, but total glutathione content and catalase activity of cells did not change. The data obtained in this study suggest that, in accordance with our previous results with fibroblast cells, CPFX-induced cytotoxicity is related to oxidative stress. And the biphasic effect of CPFX possibly resulted from the complex dose-dependent relationships between reactive oxygen species, cell proliferation, and cell viability. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:54 / 61
页数:8
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