Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kong-Jiang Road, Shanghai, 200092, China.
Biol Trace Elem Res. 2012 Dec;150(1-3):200-7. doi: 10.1007/s12011-012-9506-6. Epub 2012 Sep 16.
Metal-on-metal hip arthroplasty has been performed with increasing frequency throughout the world, particularly in younger and more active patients, including women of childbearing age. The potential toxicity of cobalt exposure on fetus is concerned since cobalt ions generated by metal-on-metal bearings can traverse the placenta and be detected in fetal blood and amniotic fluid. This study examined the effects of cobalt exposure on early embryonic development and the mechanisms underlying its toxicity. Zebrafish embryos were exposed to a range of cobalt concentrations (0-100 mg/L) between 1 and 144 h postfertilization. The survival and early development of embryos were not significantly affected by cobalt at concentrations <100 μg/L. However, embryos exposed to higher concentrations (>100 μg/L) displayed reduced survival rates and abnormal development, including delayed hatching, aberrant morphology, retarded growth, and bradycardia. Furthermore, this study examined oxidative stress and apoptosis in embryos exposed to cobalt at concentrations of 0-500 μg/L. Lipid peroxidation levels were increased in cobalt-treated embryos at concentrations of 100 and 500 μg/L. The mRNA levels of catalase, superoxide dismutase 2, p53, caspase-3, and caspase-9 genes were upregulated in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays also revealed abnormal apoptotic signals in the brain, trunk, and tail when treated with 500 μg/L cobalt. These data suggest that oxidative stress and apoptosis are associated with cobalt toxicity in zebrafish embryos.
金属对金属髋关节置换术在全球范围内的应用越来越频繁，特别是在年轻和活跃的患者中，包括育龄妇女。由于金属对金属轴承产生的钴离子可以穿过胎盘并在胎儿血液和羊水，人们对钴暴露对胎儿的潜在毒性感到担忧。本研究探讨了钴暴露对早期胚胎发育的影响及其毒性的机制。将斑马鱼胚胎暴露于 1 至 144 小时后受精的一系列钴浓度（0-100mg/L）下。在浓度<100μg/L 的情况下，钴对胚胎的存活率和早期发育没有显著影响。然而，暴露于较高浓度（>100μg/L）的胚胎存活率降低，发育异常，包括孵化延迟、形态异常、生长迟缓以及心动过缓。此外，本研究还检查了暴露于 0-500μg/L 钴浓度下的胚胎中的氧化应激和细胞凋亡。在浓度为 100 和 500μg/L 的钴处理胚胎中，脂质过氧化水平增加。过氧化氢酶、超氧化物歧化酶 2、p53、caspase-3 和 caspase-9 基因的 mRNA 水平呈剂量依赖性上调。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记测定还显示，在处理 500μg/L 钴时，大脑、躯干和尾部出现异常凋亡信号。这些数据表明，氧化应激和细胞凋亡与斑马鱼胚胎中的钴毒性有关。
