Kempka G, Ahr H J, Rüther W, Schlüter G
Bayer AG, Research Toxicology, Wuppertal, Germany.
Toxicol In Vitro. 1996 Dec;10(6):743-54. doi: 10.1016/s0887-2333(96)00050-1.
Achilles tendon rupture is known to occur after administration of various drugs to patients. It is also reported to occur after treatment with fluoroquinolone and glucocorticoids. To study potential cytotoxic effects of fluoroquinolones (ciprofloxacin, pefloxacin, sparfloxacin) and triamcinolonacetonide on tendons an in vitro model of cultivated tendon cells (human, dog, mini-pig, rat, marmoset) was established. The cells were characterized by their morphological appearance and by the synthesis of proteoglycans and collagen type I. The cytotoxicity of the tested drugs was determined by measurement of mitochondrial dehydrogenase activity (MTT assay) and other parameters (viability, proteoglycan content, proliferation). These investigations revealed the following: (1) no marked differences were found between various species after ciprofloxacin treatment, only rat tendon cells reacted slightly less sensitively at the highest concentration (100 mug/ml); (2) no age-dependent effects of ciprofloxacin and triamcinolonacetonide were found in cultivated human tendon cells from patients of different ages; (3) the simultaneous administration of fluoroquinolones and triamcinolonacetonide resulted in a significantly greater reduction of cell viability than when they were administered alone. This could indicate that the combined administration of fluoroquinolones and glucocorticoids can favour the occurrence of tendon rupture.
已知在给患者使用各种药物后会发生跟腱断裂。据报道,在使用氟喹诺酮类药物和糖皮质激素治疗后也会发生跟腱断裂。为了研究氟喹诺酮类药物(环丙沙星、培氟沙星、司帕沙星)和曲安奈德对肌腱的潜在细胞毒性作用,建立了培养肌腱细胞(人、犬、小型猪、大鼠、狨猴)的体外模型。通过细胞的形态外观以及蛋白聚糖和I型胶原的合成来对细胞进行表征。通过测量线粒体脱氢酶活性(MTT法)和其他参数(活力、蛋白聚糖含量、增殖)来确定受试药物的细胞毒性。这些研究结果如下:(1)环丙沙星治疗后不同物种之间未发现明显差异,仅大鼠肌腱细胞在最高浓度(100μg/ml)时反应稍不敏感;(2)在来自不同年龄患者的培养人肌腱细胞中未发现环丙沙星和曲安奈德有年龄依赖性影响;(3)氟喹诺酮类药物和曲安奈德同时给药导致细胞活力的降低明显大于单独给药时。这可能表明氟喹诺酮类药物和糖皮质激素联合给药会增加肌腱断裂发生的可能性。