Egerbacher M, Edinger J, Tschulenk W
Institute of Histology & Embryology, University of Veterinary Medicine, Vienna, Austria.
Am J Vet Res. 2001 May;62(5):704-8. doi: 10.2460/ajvr.2001.62.704.
To study chondrotoxic effects of enrofloxacin (ENR) and ciprofloxacin hydrochloride (CFX) on canine and equine articular chondrocytes in culture and to compare the effects with that of cultivation in Mg2+-free medium.
Chondrocytes from articular cartilage of 4- and 6 -month old dogs and 2- to 4- year-old horses.
Chondrocytes were cultivated with 10, 40, 80, and 160 microg of CFX/ml, 10, 50, 100, and 150 microg of ENR/ml, or in Mg2+-free medium. A live-to-dead test was performed to test cytotoxic effects. Morphologic changes were evaluated by electron microscopy. An attachment assay was used to test the ability of chondrocytes to adhere to collagen type-II coated-chamber slides in the presence of CFX and with Mg2+-free medium.
Chondrocytes cultivated in quinolone-supplemented medium or Mg2+-free medium had a decreased ability to adhere to culture dishes. Cell shape and the actin and vimentin cytoskeleton changed in a concentration-dependent manner. These effects were not species-specific and developed with both quinolones. On day 1 of culture, adhesion of chondrocytes to collagen type II was reduced to 70 and 45% of control values in the CFX treatment and Mg2+-free treatment groups, respectively. On day 5 of culture, adhesion of chondrocytes was reduced to 45 and 40% of control values in the CFX treatment and Mg2+-free treatment groups, respectively.
In vitro, chondrotoxic effects of quinolones appear to be the result of irregular integrin signaling and subsequent cellular changes. Drug concentrations leading to morphologic changes in vitro may be achieved in articular cartilage in vivo.
研究恩诺沙星(ENR)和盐酸环丙沙星(CFX)对犬和马培养关节软骨细胞的软骨毒性作用,并将其与在无镁培养基中培养的效果进行比较。
4月龄和6月龄犬以及2至4岁马的关节软骨细胞。
软骨细胞分别用10、40、80和160微克/毫升CFX、10、50、100和150微克/毫升ENR培养,或在无镁培养基中培养。进行活死细胞检测以测试细胞毒性作用。通过电子显微镜评估形态学变化。使用贴壁试验检测软骨细胞在CFX存在及无镁培养基条件下黏附于II型胶原包被的培养室玻片的能力。
在添加喹诺酮的培养基或无镁培养基中培养的软骨细胞黏附于培养皿的能力下降。细胞形状以及肌动蛋白和波形蛋白细胞骨架呈浓度依赖性变化。这些影响并非物种特异性,两种喹诺酮都会产生。在培养第1天,CFX处理组和无镁处理组中软骨细胞与II型胶原的黏附分别降至对照值的70%和45%。在培养第5天,CFX处理组和无镁处理组中软骨细胞的黏附分别降至对照值的45%和40%。
在体外,喹诺酮类药物的软骨毒性作用似乎是整合素信号异常及随后细胞变化的结果。体内关节软骨中可能会达到导致体外形态学变化的药物浓度。