Abstract

Nano-titanium nitride (Nano-TiN) has strong resistance to wear and corrosion, good biocompatibility, and an attractive metallic luster. Nano-TiN is widely used in medical devices, such as orthopedic implants, syringe needles, coronary stents, and long-term dental implants, and also in imitation gold jewelry. Despite its widespread use, there are few reports describing safety evaluations of Nano-TiN. Here, we exposed healthy zebrafish embryos to different concentrations of Nano-TiN solution for five days, starting at about four hours post fertilization, and found that Nano-TiN caused dose- and time-dependent developmental toxicity. With increasing Nano-TiN concentration and length of exposure, mortality, and deformities gradually increased; body length shortened and hatching rate and motility were significantly reduced. We also found that exposure to Nano-TiN affected development of the heart, liver, nerves, and other organs, and led to elevated levels of reactive oxygen species and reduced antioxidant capacity. Exposure to Nano-TiN resulted in downregulation of expression of antioxidant genes, such as nrf2, gclc, gclm, ho-1, and nqo1. Our results showed that exposure to Nano-TiN caused developmental and organ toxicity in zebrafish embryos and that the toxic effects may be mediated through oxidative stress.

摘要

纳米氮化钛（Nano-TiN）具有很强的耐磨性和耐腐蚀性，良好的生物相容性以及有吸引力的金属光泽。纳米TiN广泛用于医疗设备，例如整形外科植入物，注射器针头，冠状动脉支架和长期牙科植入物，以及人造金首饰。尽管已广泛使用，但很少有报道描述纳米TiN的安全性评估。在这里，我们将健康的斑马鱼胚胎在受精后约四小时开始，以不同浓度的Nano-TiN溶液暴露了五天，发现Nano-TiN引起了剂量和时间依赖性的发育毒性。随着纳米TiN浓度和暴露时间的增加，死亡率和畸形逐渐增加；体长缩短，孵化率和活力明显降低。我们还发现，暴露于纳米TiN会影响心脏，肝脏，神经和其他器官的发育，并导致活性氧水平升高和抗氧化能力下降。暴露于纳米TiN中会导致抗氧化基因表达的下调，例如nrf2，gclc，gclm，ho-1和nqo1。我们的结果表明，暴露于纳米TiN会引起斑马鱼胚胎的发育和器官毒性，并且其毒性作用可能是通过氧化应激介导的。