Diminished ciprofloxacin-induced chondrotoxicity by supplementation with magnesium and vitamin E in immature rats.
Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has been demonstrated previously. Identical damages can be induced in immature rats by feeding them a magnesium-deficient diet. The objective of the present study was to investigate whether, in reverse, oral supplementation with magnesium, vitamin E, or both can diminish the typical quinolone-induced arthropathy in juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats were each fed either normal feed (group A), a vitamin E-enriched diet (group B), a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats were sacrificed and cartilage samples from knee joints were examined under a light microscope for the presence of typical quinolone-induced joint cartilage lesions. In addition, magnesium, calcium, and vitamin E concentrations in cartilage and plasma were determined. In the samples from rats fed a normal diet (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups fed an enriched diet, the incidence of specific lesions (n) was significantly lower: group B, n = 10 (41% reduction compared to the incidence for group A; P < 0.05); group C, n = 6 (65% reduction; P < 0.01); and group D, n = 3 (82% reduction; P < 0.01). In comparison to the standard diet, diets with magnesium and vitamin E supplementation resulted in significantly higher magnesium and vitamin E concentrations in plasma and articular cartilage. Supplementation with magnesium and vitamin E alone or in combination may relevantly diminish joint cartilage lesions induced by quinolones in immature rats, with an additive effect of combined supplementation. The data further support the proposed pathomechanism of quinolone-induced arthropathy and the crucial role of magnesium in immature joint cartilage.
Pfister
Kerstin
K
Institut für Klinische Pharmakologie und Toxikologie, Charité CBF, Abt. Toxikologie, Garystrasse 5, 14195 Berlin, Germany.
Mazur
Dago
D
Vormann
Jürgen
J
Stahlmann
Ralf
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002118:Calcium / Q000097:blood; D002356:Cartilage / Q000473:pathology; D002357:Cartilage Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D002939:Ciprofloxacin / Q000633:toxicity*; D004032:Diet; D005260:Female; D007596:Joints / Q000473:pathology; D008274:Magnesium / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014815:Vitamins; D014810:Vitamin E; D002939:Ciprofloxacin; D008274:Magnesium; D002118:Calcium