Cytotoxic and Genotoxic Effects of Fluconazole on African Green Monkey Kidney (Vero) Cell Line

被引:12
作者
dos Santos Correa, Regianne Maciel [1 ]
Mota, Tatiane Cristina [1 ]
Guimaraes, Adriana Costa [1 ]
Bonfim, Lais Teixeira [1 ]
Burbano, Rommel Rodriguez [1 ]
Bahia, Marcelo de Oliveira [1 ]
机构
[1] Univ Fed Para, Inst Ciencias Biol, Lab Citogenet Humana, Belem, Para, Brazil
关键词
N-DEACETYL KETOCONAZOLE; PRIMARY CULTURE-SYSTEM; INDUCED HEPATOTOXICITY; OXIDATIVE STRESS; DNA; DAMAGE; ITRACONAZOLE; ACTIVATION; APOPTOSIS; DEATH;
D O I
10.1155/2018/6271547
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Fluconazole is a broad-spectrum triazole antifungal that is well-established as the first-line treatment for Candida albicans infections. Despite its extensive use, reports on its genotoxic/mutagenic effects are controversial; therefore, further studies are needed to better clarify such effects. African green monkey kidney (Vero) cells were exposed in vitro to different concentrations of fluconazole and were then evaluated for different parameters, such as cytotoxicity (MTT/cell death by fluorescent dyes), genotoxicity/mutagenicity (comet assay/micronucleus test), and induction of oxidative stress (DCFH-DA assay). Fluconazole was used at concentrations of 81.6, 163.2, 326.5, 653, 1306, and 2612.1 mu M for the MTT assay and 81.6, 326.5, and 1306 mu M for the remaining assays. MTT results showed that cell viability reduced upon exposure to fluconazole concentration of 1306 mu M (85.93%), being statistically significant (P<0.05) at fluconazole concentration of 2612.1 mu M (35.25%), as compared with the control (100%). Fluconazole also induced necrosis (P<0.05) in Vero cell line when cells were exposed to all concentrations (81.6, 326.5, and 1306 mu M) for both tested harvest times (24 and 48 h) as compared with the negative control. Regarding genotoxicity/mutagenicity, results showed fluconazole to increase significantly (P<0.05) DNA damage index, as assessed by comet assay, at 1306 mu M versus the negative control (DI=1.17 vs DI=0.28, respectively). Micronucleus frequency also increased until reaching statistical significance (P<0.05) at 1306 mu M fluconazole (with 42MN/1000 binucleated cells) as compared to the negative control (13MN/1000 binucleated cells). Finally, significant formation of reactive oxygen species (P<0.05) was observed at 1306 mu M fluconazole vs the negative control (OD=40.9 vs OD=32.3, respectively). Our experiments showed that fluconazole is cytotoxic and genotoxic in the assessed conditions. It is likely that such effects may be due to the oxidative properties of fluconazole and/or the presence of FMO (flavin-containing monooxygenase) in Vero cells.
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页数:7
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