Pfister Kerstin, Mazur Dago, Vormann Jürgen, Stahlmann Ralf
Institut für Klinische Pharmakologie und Toxikologie, Charité CBF, Abt. Toxikologie, Garystrasse 5, 14195 Berlin, Germany.
Antimicrob Agents Chemother. 2007 Mar;51(3):1022-7. doi: 10.1128/AAC.01175-06. Epub 2007 Jan 8.
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.
喹诺酮类药物对幼年大鼠及其他多种物种的软骨毒性此前已有报道。给未成熟大鼠喂食缺镁饮食可诱发相同损伤。本研究的目的是探讨相反情况下，口服补充镁、维生素E或两者能否减轻喹诺酮类药物诱发的幼年Wistar大鼠典型关节病。将四组每组12只（6只雄性，6只雌性）24日龄的Wistar大鼠分别喂食正常饲料（A组）、富含维生素E的饲料（B组）、富含镁的饲料（C组）或同时富含维生素E和镁的饲料（D组），持续10天。所有大鼠在出生后第32天接受两次皮下注射环丙沙星，剂量为600 mg/kg体重。两天后，处死大鼠，取膝关节软骨样本，在光学显微镜下检查是否存在典型的喹诺酮类药物诱发的关节软骨损伤。此外，还测定了软骨和血浆中的镁、钙和维生素E浓度。在喂食正常饮食的大鼠（A组）样本中，观察到17例喹诺酮类药物诱发的关节软骨损伤。在喂食强化饮食的组中，特定损伤的发生率（n）显著降低：B组，n = 10（与A组发生率相比降低41%；P < 0.05）；C组，n = 6（降低65%；P < 0.01）；D组，n = 3（降低82%；P < 0.01）。与标准饮食相比，补充镁和维生素E的饮食导致血浆和关节软骨中的镁和维生素E浓度显著升高。单独或联合补充镁和维生素E可能会显著减轻未成熟大鼠中喹诺酮类药物诱发的关节软骨损伤，联合补充具有相加作用。这些数据进一步支持了喹诺酮类药物诱发关节病的发病机制假说以及镁在未成熟关节软骨中的关键作用。
