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首页> 外文期刊>Journal of applied toxicology >Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells
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Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells

机译：喹诺酮左氧氟沙星对兔半月板细胞的细胞毒作用

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摘要

Quinolones have been reported to induce adverse effects on articular cartilage, tendons and ligaments. However, the effects of quinolones on menisci have not been revealed. The present study was to test the effects of levofloxacin on meniscus cells in vitro. Rabbit meniscus cells were administrated with different concentrations of levofloxacin (0, 14, 28, 56, 112 and 224μm) for 24 or 48h, and cell viability and apoptosis were measured. The mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-3, Col1a1, Bcl-2, caspase-3 and inducible nitric oxide were analyzed by real-time polymerase chain reaction. Active caspase-3 was detected by immunocytochemical assay, while protein expression levels of MMP-3 and MMP-13 were measured by Western blotting assay. After treatment with levofloxacin for 48h, cell viability was decreased from dose of 28 to 224μm in a concentration-dependent manner. An increase of apoptotic cells was observed by flow cytometry. Active caspase-3 protein expression level was also increased. The mRNA level of Bcl-2 was decreased and levels of MMP-1, MMP-3 and MMP-13 in experimental groups were higher than those of controls. The protein levels of MMP-3 and MMP-13 were increased. Moreover, the mRNA levels of TIMP-3 and col1a1 were decreased. A dose-dependent increase of inducible nitric oxide mRNA expression level was also observed. Our results suggested the cytotoxic effects of levofloxacin on meniscus cells through induction of apoptosis and unbalanced MMPs/TIMPs expression. These side effects might result in meniscus extracellular matrix degradation and meniscal lesion. Thus, quinolones should be used cautiously on patients who perform athletic activities or undergo surgical meniscus repair.
机译：据报道，喹诺酮类药物对关节软骨，肌腱和韧带产生不利影响。但是，喹诺酮类药物对半月板的作用尚未发现。本研究旨在测试左氧氟沙星在体外对半月板细胞的影响。兔半月板细胞经不同浓度的左氧氟沙星（0、14、28、56、112和224μm）给药24h或48h，并测量细胞活力和凋亡。分析了基质金属蛋白酶（MMP）-1，MMP-3，MMP-13，金属蛋白酶组织抑制剂（TIMP）-1，TIMP-3，Col1a1，Bcl-2，caspase-3和诱导型一氧化氮的mRNA表达水平。通过实时聚合酶链反应。通过免疫细胞化学法检测活性caspase-3，同时通过蛋白质印迹法检测MMP-3和MMP-13的蛋白表达水平。左氧氟沙星处理48h后，细胞存活率以剂量依赖性方式从28降低到224μm。通过流式细胞术观察到凋亡细胞的增加。活性caspase-3蛋白表达水平也有所提高。实验组Bcl-2 mRNA水平下降，MMP-1，MMP-3和MMP-13水平明显高于对照组。 MMP-3和MMP-13的蛋白质水平增加。此外，TIMP-3和col1a1的mRNA水平下降。还观察到诱导型一氧化氮mRNA表达水平的剂量依赖性增加。我们的结果表明左氧氟沙星通过诱导凋亡和不平衡的MMP / TIMPs表达对半月板细胞产生细胞毒性作用。这些副作用可能导致半月板细胞外基质降解和半月板病变。因此，在进行体育活动或进行半月板手术的患者应谨慎使用喹诺酮类药物。

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