R. Stahlmann et al., Effects of magnesium deficiency on joint cartilage in immature Beagle dogs: immunohistochemistry, electron microscopy, and mineral concentrations, ARCH TOXIC, 73(10-11), 2000, pp. 573-580
Quinolone-induced chondrotoxicity is possibly associated with the magnesium
-chelating properties of quinolones. This toxic effect seems to be restrict
ed to a rather short rime period during postnatal development as shown in r
ats and dogs. We studied developmental changes of the integrin pattern on c
anine 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 matr
ix composition (e.g., collagen type II, fibronectin), in 11-, 18-, and 55-w
eek-old Beagles (n = 8) by immunohistochemistry. We also analyzed the magne
sium and calcium content by atomic absorption spectroscopy in cartilage and
bone and studied the effects of a magnesium-deficient diet on joint cartil
age 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 alt
erations ('limping') after 4 weeks on the magnesium-deficient diet. Male, m
agnesium-deficient dogs exhibited pronounced weakness in their front legs;
in one of these dogs the front legs were hyperextended to a 90 degrees angl
e. We observed no significant differences in the integrin pattern in sample
s from dogs at different developmental stages or in magnesium-deficient dog
s 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, co
rresponding to the predilective site of quinolone-induced cartilage lesions
, we observed a slight increase in staining with the fibronectin antibody i
n some samples from magnesium-deficient dogs. Electron microscopy revealed
alterations in chondrocytes from the magnesium-deficient dogs (e.g., swolle
n mitochondria and enlarged endoplasmic reticulum) which are also seen afte
r treatment with quinolones. In summary, we found no significant difference
s of the integrin pattern on chondrocytes from joint cartilage of dogs at v
arious developmental stages. However, magnesium deficiency in immature dogs
induced similar clinical symptoms as quinolone treatment as well as distin
ct alterations in chondrocytic fibronectin staining and their ultrastructur
e. This corroborates our findings in rats where magnesium chelation is an i
mportant event in quinolone-induced chondrotoxicity.