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Toxicologic Pathology
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Comparative Evaluation of Ultrastructural Changes in Articular Cartilage of Ofioxacin-Treated and Magnesium-Deficient Immature Rats

Mehdi Shakibaei

Institut für Anatomie, Freie Universität Berlin, Berlin, FRG

Katja Kociok

Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Berlin, FRG

Christian Förster

Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Berlin, FRG

Jürgen Vormann

Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Berlin, FRG

Theodor Günther

Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Berlin, FRG

Ralf Stahlmann

Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Berlin, FRG

Hans-Joachim Merker

Institut für Anatomie, Freie Universität Berlin, Berlin, FRG, Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Berlin, FRG

Ultrastructural changes in immature articular cartilage were studied after treatment of 5-wk-old rats with ofloxacin—a fluoroquinolone—and in magnesium deficiency. Magnesium deficiency was induced by feeding a magnesium-deficient diet for 9 days; the condition was confirmed by measuring the concentrations of the mineral in plasma, bone, and cartilage samples of the animals by atomic absorption spectrophotometry. Oral administration of single doses of 600 or 1,200 mg ofloxacin/kg body weight and magnesium deficiency were sufficient to induce gross structural cartilage defects. Alterations observed on the ultrastructural level showed striking similarities in magnesium-deficient rats and in rats treated with single doses of 600 mg ofloxacin/kg body weight. Typical observations were (a) bundle-shaped, electron-dense aggregates on the surface and in the cytoplasm of chondrocytes, (b) detachment of the cell membrane from the matrix and necrotic chondrocytes, (c) reduction of the extracellular matrix, and (d) swelling of cell organelles such as mitochondria. These findings further substantiate the histological finding that quinolone treatment and a dietarily induced magnesium-deficiency induce indistinguishable pathological conditions in immature joint cartilage, and they suggest that quinolone-induced arthropathy is probably caused by a reduction of functionally available magnesium (ionized Mg2+) in cartilage (42). Furthermore, they provide a basis for aimed studies with human cartilage samples from quinolone-treated patients that might be available postmortally or after hip replacement surgery.

Key Words: Quinolone-induced arthropathy • magnesium • electron microscopy • chondrocytes

Toxicologic Pathology, Vol. 24, No. 5, 580-587 (1996)
DOI: 10.1177/019262339602400507


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