Effects of magnesium deficiency on joint cartilage in immature beagle dogs: immunohistochemistry, electron microscopy, and mineral concentrations.
Quinolone-induced chondrotoxicity is possibly associated with the magnesium-chelating properties of quinolones. This toxic effect seems to be restricted to a rather short time period during postnatal development as shown in rats and dogs. We studied developmental changes of the integrin pattern on canine chondrocytes (e.g. the alpha(v)beta(3)- or alpha(5)beta(1)-integrin), because integrin function depends on divalent cations, as well as the matrix composition (e.g., collagen type II, fibronectin), in 11-, 18-, and 55-week-old Beagles (n=8) by immunohistochemistry. We also analyzed the magnesium and calcium content by atomic absorption spectroscopy in cartilage and bone and studied the effects of a magnesium-deficient diet on joint cartilage in four immature Beagles (18 weeks old at necropsy). The dogs were fed the magnesium-deficient diet for 40 to 46 days. All dogs exhibited gait alterations ('limping') after 4 weeks on the magnesium-deficient diet. Male, magnesium-deficient dogs exhibited pronounced weakness in their front legs; in one of these dogs the front legs were hyperextended to a 90 degrees angle. We observed no significant differences in the integrin pattern in samples from dogs at different developmental stages or in magnesium-deficient dogs in comparison to age-matched controls. Localization of fibronectin in the joint cartilage was found to vary with the age of the dogs as well as with the site of collection. In the middle zone of immature joint cartilage, corresponding to the predilective site of quinolone-induced cartilage lesions, we observed a slight increase in staining with the fibronectin antibody in some samples from magnesium-deficient dogs. Electron microscopy revealed alterations in chondrocytes from the magnesium-deficient dogs (e.g., swollen mitochondria and enlarged endoplasmic reticulum) which are also seen after treatment with quinolones. In summary, we found no significant differences of the integrin pattern on chondrocytes from joint cartilage of dogs at various developmental stages. However, magnesium deficiency in immature dogs induced similar clinical symptoms as quinolone treatment as well as distinct alterations in chondrocytic fibronectin staining and their ultrastructure. This corroborates our findings in rats where magnesium chelation is an important event in quinolone-induced chondrotoxicity.
Stahlmann
R
R
Institut für Klinische Pharmakologie und Toxikologie, Abteilung Toxikologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Garystr. 5, 14195 Berlin, Germany.
Kühner
S
S
Shakibaei
M
M
Flores
J
J
Vormann
J
J
van Sickle
D C
DC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019902:Chondrocytes / Q000378:metabolism / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism; D004032:Diet; D004285:Dogs; D005260:Female; D005270:Femur Head / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005684:Gait / Q000502:physiology; D016023:Integrins / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008274:Magnesium / Q000378:metabolism; D008275:Magnesium Deficiency / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D013054:Spectrophotometry, Atomic
D005353:Fibronectins; D016023:Integrins; D003094:Collagen; D008274:Magnesium; D002118:Calcium