首页> 外文期刊>European Journal of Pharmacology: An International Journal >Ofloxacin induces oxidative damage to joint chondrocytes of juvenile rabbits: excessive production of reactive oxygen species, lipid peroxidation and DNA damage.
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Ofloxacin induces oxidative damage to joint chondrocytes of juvenile rabbits: excessive production of reactive oxygen species, lipid peroxidation and DNA damage.

机译:氧氟沙星会诱导幼兔关节软骨细胞的氧化损伤:活性氧的过度产生,脂质过氧化和DNA损伤。

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摘要

Quinolones are widely used in infection therapy due to their good antimicrobial characteristics. However, there potential joint chondrotoxicity on immature animals has stood in the way of the therapeutic application of these agents, the exact mechanism of which is still unclear. This study was undertaken to investigate the role of oxidative damage in ofloxacin (one typical quinolones)-induced arthropathy. Chondrocytes from juvenile rabbit joints were incubated with ofloxacin at concentrations of 0, 5, 10, 20, 40 and 80 microg/ml, respectively. The extent of oxidative damage was assessed by measuring the reactive oxygen species level, activities of antioxidant enzymes, and oxidative damage to some macromolecules. It was observed that ofloxacin induced a concentration-dependent increase in intracellular reactive oxygen species production, which may be an early mediator of ofloxacin cytotoxicity. Similarly, ofloxacin resulted in a significant lipid peroxidation, revealed by a concentration-dependent increase in the level of thiobarbituric acid reactive substances. At the same time, ofloxacin induced DNA damage in a concentration-dependent manner for 24h measured by comet assay, which may be a cause for overproduction of reactive oxygen species. Furthermore, antioxidant enzyme activities, such as glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD), were rapidly decreased after treatment with ofloxacin. In addition, SOD decline and reactive oxygen species production were strongly inhibited, and the loss in cell viability was partly abated by additional glutathione (GSH), N-acetylcysteine (NAC) and dithiothreitol (DTT). In conclusion, these results clearly demonstrated that ofloxacin could induce oxidative stress, lipid peroxidation and DNA oxidative damage to chondrocytes.
机译:喹诺酮类药物具有良好的抗菌特性,被广泛用于感染治疗。然而,未成熟动物可能存在关节软骨毒性,阻碍了这些药物的治疗应用,其确切机制仍不清楚。进行这项研究以研究氧化损伤在氧氟沙星(一种典型的喹诺酮类药物)诱发的关节炎中的作用。将来自幼兔关节的软骨细胞分别与浓度为0、5、10、20、40和80微克/毫升的氧氟沙星一起孵育。通过测量活性氧水平,抗氧化酶的活性以及对某些大分子的氧化损伤来评估氧化损伤的程度。观察到氧氟沙星诱导细胞内活性氧产生的浓度依赖性增加,这可能是氧氟沙星细胞毒性的早期介质。类似地,氧氟沙星导致明显的脂质过氧化,这是由硫代巴比妥酸反应性物质的浓度依赖性增加所揭示的。同时,氧氟沙星通过彗星测定法以浓度依赖性方式诱导DNA损伤24小时,这可能是活性氧过高产生的原因。此外,氧氟沙星治疗后抗氧化酶活性迅速降低,例如谷胱甘肽过氧化物酶(GPx),过氧化氢酶和超氧化物歧化酶(SOD)。此外,SOD的下降和活性氧的产生受到强烈抑制,细胞活力的丧失可通过额外的谷胱甘肽(GSH),N-乙酰半胱氨酸(NAC)和二硫苏糖醇(DTT)得以部分缓解。总之,这些结果清楚地表明氧氟沙星可以诱导软骨细胞氧化应激,脂质过氧化和DNA氧化损伤。

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