Effects of Difloxacin on the Metabolism of Glycosaminoglycans and Collagen in Organ Cultures of Articular Cartilage

Fluoroquinolones, including difloxacin, are potent antibacterialcompounds which, as a side effect, cause lesions in articular-epiphysealcartilage complexes (AECC) of growing animals. To evaluate theeffects of difloxacin on the structure of AECC and the metabolismof sulfated glycosaminoglycans (GAG) and collagen, explantsof AECC were obtained from 18 healthy, 3-month-old Beagle dogsand cultured in medium which either had no difloxacin or hadthe drug at one of three concentrations (40, 80, or 160 µg/ml).Rates of synthesis of GAG and collagen were reduced by concentrationsof difloxacin that were at or above 80 µg/ml. The rateof synthesis of total protein, however, was reduced only atthe highest dose level. Catabolism of GAG and collagen was unaffectedby the treatment. The principal ultrastructural changes in affectedchondrocytes were distension of rough endoplasmic reticulumwith electron-dense material that was probably protein, andvacuolation of cytoplasm. Structural changes were not observedin the extracellular matrix. It, therefore, appeared plausiblethat difloxacin affected chondrocytes by interfering with secretionof the matrix components, GAG and collagen.