Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596

• Published in: Experimental and toxicologic pathology (Print) Vol. 48; no. 4; pp. 225 - 232
• Main Authors: Gough, A., Johnson, R., Campbell, E., Hall, L., Tylor, J., Carpenter, A., Black, W., Basrur, P.K., Baragi, V.M., Sigler, R., Metz, A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Jena Elsevier GmbH 01-06-1996; Elsevier
• Subjects: Animals; Anti-Infective Agents - toxicity; Arthritis - chemically induced; Arthritis - pathology; Arthropathy, quinolone; Articular cartilage; Biological and medical sciences; Cartilage, Articular - drug effects; Cartilage, Articular - pathology; Cartilage, Articular - ultrastructure; Disease Models, Animal; Drug toxicity and drugs side effects treatment; Fluoroquinolone, PD 117596; Fluoroquinolones; Knee Joint - drug effects; Knee Joint - pathology; Knee Joint - ultrastructure; Magnetic Resonance Imaging; Male; Medical sciences; Pharmacology. Drug treatments; Quinolone antibacterials; Quinolone arthropathy; Quinolones - adverse effects; Rabbits; Toxicity: osteoarticular system; Xenobiotic-induced arthropathy; Xenobiotic-induced arthropathy; Articular cartilage; Magnetic resonance imaging; Fluoroquinolone, PD 117596; Arthropathy, quinolone; Quinolone arthropathy; Quinolone antibacterials; Fluoroquinolone derivative; Toxicity; Diseases of the osteoarticular system; Oral administration; Rabbit; Lagomorpha; Nuclear magnetic resonance imaging; Pathology; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Animal; Arthropathy; Dose; Comparative study
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/S0940-2993(96)80003-0

To study the potential of the fluorquinolone, PD 117596 to cause arthropathy in experimental animals, immature rabbits were orally administered the drug for five days at 0, 100, 350, 500 and 750 mg/kg. Characterization of changes induced in major synovial joints was based on: macroscopic and histopathologic observations, transmission electron microscopic examinations and magnetic resonance imaging. Preferentially targeting the knee, PD 117596 produced vesicles and erosions in articular cartilage which resembled, morphologically, those described in other laboratory species. Lesion incidence was not clearly dose-related. In the perivesicular region, degenerate chondrocytes were intermixed with hypertrophic cartilage cells and chondrocyte clusters. Ultrastructurally, hypertrophic chondrocytes were the consequence of karyomegaly and RER proliferation. Matrix density was reduced due to collagen and proteoglycan loss. Joint structures were readily visualized by magnetic resonance imaging which identified thickened articular cartilage, surface irregularities consistent with ruptured vesicles and separation of opposing articular surfaces secondary to synovival effusions. The immature rabbit, although less sensitive than the juvenile dog to the arthropathic effects of quinolones, was nonetheless a good model to study this experimental osteoarticular disease.