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Immunohistochemistry of Articular Cartilage from Immature Beagle Dogs Dosed with DifloxacinPfizer Central Research, Drug Safety Evaluation, Groton, Connecticut 06340, USA, John_E_Burkhardt{at}groton.pfizer.com
Institut fur Klinische Pharmakologie und Toxikologie, Freien Universitat Berlin Garystr. 5, 14195 Berlin, Germany
Institut fur Klinische Pharmakologie und Toxikologie, Freien Universitat Berlin Garystr. 5, 14195 Berlin, Germany
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, USA
Institut fur Klinische Pharmakologie und Toxikologie, Freien Universitat Berlin Garystr. 5, 14195 Berlin, Germany
Effects of the fluoroquinolone difloxacin on articular-epiphyseal cartilage in growing beagle dogs have been described by light microscopic, electron microscopic, and biochemical methods. Here we present data from an immunohistochemistry study with humeral head cartilage from 3-mo-old beagle dogs after treatment with 1 or 2 oral doses of 300 mg difloxacin/kg body weight. Dogs were euthanatized either 24 hr (single dose) or 48 hr (2 doses) after onset of dosing, and cartilage tissue was stored at -90°C until it was studied by immunohistochemistry. Antibodies against matrix components (collagen II, fibronectin) as well as antibodies against cellular structures (integrins) were used. After single-dose treatment (24-hr group), cartilage lesions such as clefts were not observed, but increased staining for fibronectin was found in cartilage samples from 5 of 6 animals. Markedly increased staining for fibronectin was also demonstrated in the vicinity of clefts within cartilage of all animals of the 48-hr group. Collagen II staining was homogeneously distributed in cartilage from controls and was slightly reduced in territorial matrix in 2 of 6 dogs of the 48-hr group. Integrin staining on chondrocytes was not significantly affected by difloxacin under the given conditions with the exception of a slight reduction of the
Key Words: Quinolone-induced arthropathy • fibronectin • collagen • integrins
Toxicologic Pathology, Vol. 25, No. 5,
475-480 (1997) This article has been cited by other articles:
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v integrin chain in 1 of 5 dogs of the 48-hr group. Overall, the most important result is the finding that fibronectin was a sensitive immunohistochemical marker for change in cartilage samples due to difloxacin treatment in dogs. 
