Immunohistochemistry of articular cartilage from immature beagle dogs dosed with difloxacin.
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 degrees 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 alpha v integrin chain in 1 of 5 dogs of the 48-hr group. Overall, the most important results is the finding that fibronectin was a sensitive immunohistochemical marker for change in cartilage samples due to difloxacin treatment in dogs.
Burkhardt
J E
JE
Pfizer Central Research, Drug Safety Evaluation, Groton, Connecticut 06340, USA. John_E_Burkhardt@groton.pfizer.com
Förster
C
C
Lozo
E
E
Hill
M A
MA
Stahlmann
R
R
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D015703:Antigens, CD / Q000378:metabolism; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000633:toxicity; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D024841:Fluoroquinolones; D006811:Humerus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D039564:Integrin alphaV
D000890:Anti-Infective Agents; D015703:Antigens, CD; D005353:Fibronectins; D024841:Fluoroquinolones; D039564:Integrin alphaV; D002939:Ciprofloxacin; C047225:difloxacin; D003094:Collagen