Shakibaei M, Kociok K, Förster C, Vormann J, Günther T, Stahlmann R, Merker H J
Institut für Anatomie, Freie Universität Berlin, FRG.
Toxicol Pathol. 1996 Sep-Oct;24(5):580-7. doi: 10.1177/019262339602400507.
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.
研究了用氟喹诺酮类药物氧氟沙星治疗5周龄大鼠并使其处于镁缺乏状态后，未成熟关节软骨的超微结构变化。通过喂食缺镁饮食9天诱导大鼠镁缺乏；通过原子吸收分光光度法测量动物血浆、骨骼和软骨样本中矿物质的浓度来确认这种状态。口服单剂量600或1200毫克氧氟沙星/千克体重以及镁缺乏足以诱发明显的软骨结构缺陷。在超微结构水平上观察到的变化在缺镁大鼠和用单剂量600毫克氧氟沙星/千克体重治疗的大鼠中显示出惊人的相似性。典型的观察结果包括：(a)软骨细胞表面和细胞质中呈束状、电子致密的聚集体；(b)细胞膜与基质分离以及软骨细胞坏死；(c)细胞外基质减少；(d)细胞器如线粒体肿胀。这些发现进一步证实了组织学研究结果，即喹诺酮治疗和饮食诱导的镁缺乏在未成熟关节软骨中诱发难以区分的病理状况，并且表明喹诺酮诱导的关节病可能是由软骨中功能性可用镁（离子化Mg2+）减少引起的(42)。此外，它们为对喹诺酮治疗患者死后或髋关节置换手术后可能获得的人类软骨样本进行针对性研究提供了基础。
