Antibiotics for local delivery systems cause skeletal cell toxicity in vitro
Antibiotics for local delivery systems cause skeletal cell toxicity in vitro
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DOI：
10.1097/blo.0b013e31811ff866
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发表时间：
2007-09-01
影响因子：
4.2
通讯作者：
Parvizi, Javad
中科院分区：
文献类型：
--
作者：
Antoci, Valentin, Jr.;Adams, Christopher S.;Parvizi, Javad
与抗生素骨水泥相关的抗生素浓度可能会导致骨骼细胞毒性，并阻止骨折愈合。我们研究了骨科局部给药系统中常用的三种抗生素暴露后的剂量和治疗时间的毒性效应。我们假设在环丙沙星、万古霉素或妥布霉素治疗后，成骨细胞和软骨细胞的毒性存在一个阈值。为了验证这一假设，我们首先确定了抗生素治疗是否会导致细胞形态的差异。暴露于环丙沙星的细胞在铺展、细胞膜和伸展方面有相当大的变化。接下来，我们询问多大剂量的抗生素会导致成骨细胞和软骨细胞数量减少。环丙沙星的剂量大于100微克/毫升，万古霉素和妥布霉素的剂量大于2000微克/毫升，则严重抑制细胞的增殖。最后，我们质疑观察到的细胞数量的减少是否是细胞毒性增加或衰老的结果。成骨细胞释放的乳酸脱氢酶比例显著增加。这些数据表明，靶向杀菌效果和宿主细胞毒性之间的平衡对骨骼细胞的生存和功能至关重要。
Antibiotic concentrations associated with antibiotic bone cements may cause skeletal cell toxicity and prevent fracture healing. We investigated toxicity effects of dose and treatment time after exposure to three antibiotics commonly used in orthopaedic local drug delivery systems. We hypothesized a threshold exists for toxicity of osteoblasts and chondrocytes after treatment with ciprofloxacin, vancomycin, or tobramycin. To test this hypothesis, we first determined whether treatment with antibiotics caused differences in cellular morphology. Cells exposed to ciprofloxacin showed considerable changes in spread, cell membrane, and extensions. We next asked what dosage of antibiotic would cause reductions in osteoblast and chondrocyte cell numbers. Ciprofloxacin at a dose greater than 100 mu g/mL and vancomycin and tobramycin at doses greater than 2000 mu g/mL severely decreased cellular proliferation. Finally, we questioned whether observed decreases in cell numbers were the result of increased cellular toxicity or senescence. Released lactate dehydrogenase ratios were severely increased in osteoblasts. These data suggest the balance between the targeted microbicidal effects and host cellular toxicity is critical for skeletal cell survival and function.