Effects of difloxacin on the metabolism of glycosaminoglycans and collagen in organ cultures of articular cartilage.
Fluoroquinolones, including difloxacin, are potent antibacterial compounds which, as a side effect, cause lesions in articular-epiphyseal cartilage complexes (AECC) of growing animals. To evaluate the effects of difloxacin on the structure of AECC and the metabolism of sulfated glycosaminoglycans (GAG) and collagen, explants of AECC were obtained from 18 healthy, 3-month-old Beagle dogs and cultured in medium which either had no difloxacin or had the drug at one of three concentrations (40, 80, or 160 micrograms/ml). Rates of synthesis of GAG and collagen were reduced by concentrations of difloxacin that were at or above 80 micrograms/ml. The rate of synthesis of total protein, however, was reduced only at the highest dose level. Catabolism of GAG and collagen was unaffected by the treatment. The principal ultrastructural changes in affected chondrocytes were distension of rough endoplasmic reticulum with electron-dense material that was probably protein, and vacuolation of cytoplasm. Structural changes were not observed in the extracellular matrix. It, therefore, appeared plausible that difloxacin affected chondrocytes by interfering with secretion of the matrix components, GAG and collagen.
Burkhardt
J E
JE
Department of Veterinary Pathobiology, Purdue University, West Lafayette, Indiana 47907.
Hill
M A
MA
Lamar
C H
CH
Smith
G N
GN
Carlton
W W
WW
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D004285:Dogs; D024841:Fluoroquinolones; D006025:Glycosaminoglycans / Q000378:metabolism*; D009924:Organ Culture Techniques
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D006025:Glycosaminoglycans; C013786:A73025; D002939:Ciprofloxacin; C047225:difloxacin; D003094:Collagen