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Effects of Nalidixic Acid on Hamster Knee Cartilage Morphology and Synovial Fluid Composition

Department of Drug Safety Evaluation

James D. Eskra

Department of Respiratory, Allergy, Immunology, Inflammation, and Infectious Disease, Pfizer Central Research, Groton, Connecticut

Frances A.S. Clemo

Department of Drug Safety Evaluation

Ivan G. Otterness

Department of Respiratory, Allergy, Immunology, Inflammation, and Infectious Disease, Pfizer Central Research, Groton, Connecticut

Quinolone-induced changes were studied in the knee joints of 4-wk-old female hamsters given intraperitoneal doses of either nalidixic acid (400 mg/kg body weight) or vehicle on days 0 and 1. After euthanasia on day 4, synovial fluid was collected for cytologic evaluation and for analysis of concentrations of hyaluronan, proteoglycans, total protein, and collagen as hydroxyproline. Slides of formalin-fixed decalcified tissues were stained with hematoxylin-eosin or safranin O for histologic scoring of lesion severity. Nine of 10 hamsters treated with nalidixic acid had fissures within articular cartilage of the femur and reduced safranin O staining of matrix indicative of loss of proteoglycans. Synovial membranes from affected joints, however, were not inflamed. Synovial fluid cell counts and cytomorphology were unaffected by treatment. In synovial fluid from 5 of 10 treated hamsters, proteoglycans were elevated by more than 2 SDs above the control group, and individual animal levels correlated with the histologic severity score (r2 = 0.36; p = 0.02). The hyaluronan content of the synovial fluid from treated hamsters was mildly but significantly elevated (p = 0.005), and the histologic severity score again correlated with individual animal levels (r² = 0.42; p = 0.01). Hydroxyproline was unaffected by treatment. Although synovial fluid changes and histologic changes were correlated on a group basis, interanimal variability was significant and the magnitude of biochemical changes were far smaller than those that occur during inflammation. Changes in synovial fluid composition are not sufficiently robust to predict cartilage changes in individual animals.

Key Words: Quinolone-induced arthropathy • nalidixic acid • hamsters articular cartilage • synovial fluid • proteoglycans • collagen • hyaluronic acid

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Toxicologic Pathology, Vol. 27, No. 4, 421-426 (1999)
DOI: 10.1177/019262339902700405


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