Shakibaei M, Förster C, Merker H J, Stahlmann R
Institut für Anatomie, Freie Universität Berlin, Königin-Luise Str. 15, D-14195, Berlin, Germany.
Toxicol In Vitro. 1995 Apr;9(2):107-16. doi: 10.1016/0887-2333(94)00198-4.
Quinolone-induced arthropathy is an important toxic effect in immature animals that has led to restrictions of the therapeutic use of these antimicrobial agents. The effects of ofloxacin on epiphyseal chondrocytes from 17-day-old mouse foetuses were studied in vitro. Adhesion of the cells to culture dishes was impaired in a concentration-dependent manner and was first perceptible at a concentration of 10 mg ofloxacin/litre medium. A closer analysis by immunomorphological methods showed that the expression of several integrin receptors (beta1, alpha3, alpha5beta1, alphavbeta3) on the chondrocytes was reduced. Again, first alterations occurred at the rather low concentration of 10 mg ofloxacin/litre medium, and at 30 mg ofloxacin/litre medium alpha3- and alpha5beta1 integrins were demonstrable on 50% or less of the cultured cells. Based on these findings in vitro, a new hypothesis for the mechanism of the chondrotoxicity of quinolones is proposed: the ability of these antimicrobials to form chelate complexes with divalent cations could explain why the integrin receptors on chondrocytes are altered after quinolone exposure, since it is well known that the function of the integrin receptor depends on calcium or magnesium ions. Further investigations are under way to study the effects of quinolones on integrin receptors in cartilage in more detail.
喹诺酮类药物引起的关节病是幼龄动物的一种重要毒性作用，这已导致对这些抗菌药物治疗用途的限制。在体外研究了氧氟沙星对17日龄小鼠胎儿骨骺软骨细胞的影响。细胞对培养皿的黏附以浓度依赖的方式受损，在氧氟沙星浓度为10毫克/升培养基时首次可察觉到这种情况。通过免疫形态学方法进行的更深入分析表明，软骨细胞上几种整合素受体（β1、α3、α5β1、αvβ3）的表达减少。同样，在氧氟沙星浓度相当低（10毫克/升培养基）时就出现了最初的变化，在氧氟沙星浓度为30毫克/升培养基时，α3和α5β1整合素在50%或更少的培养细胞上可检测到。基于这些体外研究结果，提出了关于喹诺酮类药物软骨毒性机制的新假说：这些抗菌药物与二价阳离子形成螯合物的能力可以解释为什么喹诺酮类药物暴露后软骨细胞上的整合素受体会发生改变，因为众所周知整合素受体的功能依赖于钙离子或镁离子。正在进行进一步研究以更详细地研究喹诺酮类药物对软骨中整合素受体的影响。
