Chondrotoxicity of quinolones in vivo and in vitro.
Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials. To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives. The effects on cell viability, mitochondrial dehydrogenase, and proteoglycan synthesis were determined. These results were compared with in vivo findings in dogs treated with these quinolones. It was concluded that inhibition of mitochondrial dehydrogenase activity and of proteoglycan synthesis are major reasons for cartilage damage. Therefore this in vitro model is capable of identifying strongly arthropathogenic quinolones without the need of performing animal studies.
Hildebrand
H
H
Bayer AG, Fachbereich Toxikologie, Pharma-Forschungszentrum, Wuppertal, Germany.
Kempka
G
G
Schlüter
G
G
Schmidt
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002357:Cartilage Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D024841:Fluoroquinolones; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009268:Nalidixic Acid / Q000633:toxicity*; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D009268:Nalidixic Acid; D010088:Oxidoreductases