Hildebrand H, Kempka G, Schluter G, Schmidt M.

Bayer AG, Fachbereich Toxikologie, Pharma-Forschungszentrum, Wuppertal, Germany.

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.

1: Bioorg Med Chem Lett. 2000 Mar 6;10(5):443-7.