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首页> 外文期刊>Archives of Toxicology >Effects of moxifloxacin and clinafloxacin on murine limb buds cultured in regular and in magnesium-deficient medium
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Effects of moxifloxacin and clinafloxacin on murine limb buds cultured in regular and in magnesium-deficient medium

机译：莫西沙星和克林沙星对常规和缺镁培养基中培养的鼠肢芽的影响

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摘要

Evaluation of the prenatal toxicity of a substance in rats or other animals according to the current guidelines is often hampered by the rapid metabolism of the test compound and/or by maternal toxicity. One example for such a compound is moxifloxacin. In vitro systems offer the possibility to study the direct effects of the test compound on embryonic tissues. The aim of this study was to evaluate the embryotoxic potential of moxifloxacin in vitro using the murine limb bud culture. Clinafloxacin, which was found to be teratogenic when tested in rats, was used for comparison. The effects of various concentrations of moxifloxacin (10, 30, 60 and 100 mg/L) and clinafloxacin (3, 10 and 30 mg/L) on growth and differentiation of 12-day-old murine limb buds were studied in a standard and in a magnesium-deficient medium. After termination of the culture, the respective front limb buds were examined by different methods. Clinafloxacin showed clear-cut effects at a concentration of 30 mg/L in both media. Effects were similarly pronounced as the effects observed with moxifloxacin at a concentration of 100 mg/L. Lower concentrations of moxifloxacin, which are achieved during therapy in humans, did not impair growth and differentiation of limb buds. Using electron microscopy, slight ultrastructural changes could be seen after exposure to 3 mg clinafloxacin/L medium. Ultrastructurally, clinafloxacin caused a concentration-dependent decrease of the extracellular matrix, swelling of cell organelles and at higher concentrations necrotic chondrocytes. These effects were significantly enhanced in a magnesium-deficient medium. In conclusion, the effects of moxifloxacin on murine limb buds in vitro were definitely less pronounced than those of clinafloxacin. Effects on growth and differentiation occurred with moxifloxacin only at concentrations that are higher than plasma concentrations observed during therapy. This result is of special interest, because due to rapid metabolism of moxifloxacin in rats results from a routinely performed segment II type study cannot be used for a risk assessment.
机译：根据当前的指导方针，在大鼠或其他动物中评估某种物质的产前毒性通常会由于测试化合物的快速代谢和/或母体毒性而受到阻碍。这种化合物的一个例子是莫西沙星。体外系统提供了研究试验化合物对胚胎组织的直接作用的可能性。这项研究的目的是使用鼠肢芽培养物评估莫西沙星在体外的胚胎毒性潜力。使用氯那沙星在大鼠中测试时被发现具有致畸性，用于比较。以标准浓度和标准浓度研究了不同浓度的莫西沙星（10、30、60和100 mg / L）和克林沙星（3、10和30 mg / L）对12日龄鼠肢芽生长和分化的影响。在缺镁的培养基中。培养终止后，通过不同方法检查各自的前肢芽。克林沙星在两种培养基中的浓度均为30 mg / L时均表现出明显的效果。效果与在100 mg / L的莫西沙星所观察到的效果相似。在人类治疗期间达到的较低浓度的莫西沙星不会损害肢芽的生长和分化。使用电子显微镜，暴露于3 mg克林沙星/ L培养基后可观察到轻微的超微结构变化。在超微结构中，克林沙星引起浓度依赖性的细胞外基质减少，细胞器肿胀和坏死软骨细胞浓度升高。在缺镁的培养基中，这些作用显着增强。总之，莫西沙星对小鼠肢体芽的体外作用肯定不如克林沙星明显。莫西沙星仅在高于治疗期间观察到的血浆浓度时才发生对生长和分化的影响。该结果特别令人关注，因为由于莫西沙星在大鼠中的新陈代谢迅速，因此常规II段II型研究的结果不能用于风险评估。

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