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Early Pathophysiologic Feature of Arthropathy in Juvenile Dogs Induced by Ofloxacin, a Quinolone Antimicrobial Agent

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd., Kita-Kasai 1-Chome, Edogawaku, Tokyo, Japan (KY, HS, YI, TJ, TS, KF); and Department of Veterinary Pathology, Faculty of Agriculture, Iwate University, Iwate, Japan (MG, KO)

Arthropathy in dogs induced by ofloxacin, a quinolone antimicrobial agent, was pathophysiologically investigated. In the in vivo studies, ofloxacin was administered orally once or twice at 20 mg/kg/day to male juvenile (3-month-old, n = 3) or adult (36-month-old, n = 2) dogs, and the humeral and femoral heads were examined pathologically. Unlike adult dogs, fluid-filled vesicles were macroscopically observed on the articular surfaces of one juvenile dog 24 hours after a single treatment with ofloxacin. These lesions were seen in all juvenile dogs by twice dosing. Microscopically, fissures or cavity formations in the middle zone of the articular cartilage were noted only in juvenile dogs. Furthermore, the cartilage matrix from the abnormal area to the articular surface showed a decreased safranin-O staining intensity, suggesting proteoglycan depletion. Ultrastructurally, chondrocytes in the middle zone of juvenile dogs displayed dilatation of the cisternae in the rough endoplasmic reticulum as an initial hallmark. In the in vitro studies, chondrocytes isolated from the articular cartilage of naive juvenile dogs were exposed to ofloxacin at 6.3–100 µg/ml for 24 hours. Although no changes were noted in the deoxyribonucleic acid synthesis, protein synthesis, or proteoglycan release at concentrations of up to 100 µg/ml, the proteoglycan synthesis was evidently decreased in a dose-dependent manner from 12.5 µg/ml. The results obtained suggest that the inhibitory action of ofloxacin on proteoglycan syntheses in the chondrocytes may largely contribute to the early morphologic features in the articular cartilage of the juvenile dog.

Key words: Arthropathy; articular cartilage; juvenile dogs; proteoglycan; quinolone antimicrobial agent.

Request reprints from Dr. K. Yabe, Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd., 16-13, Kita-Kasai 1-Chome, Edogawaku, Tokyo 134-8630 (Japan). E-mail: yabek21l{at}daiichipharm.co.jp