Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Neurotoxicol Teratol. 2010 May-Jun;32(3):391-7. doi: 10.1016/j.ntt.2010.01.009. Epub 2010 Jan 29.
The increased use of silver nanoparticles in consumer and medical products has led to elevated human and environmental exposures. Silver nanoparticles act as antibacterial/antifungal agents by releasing Ag(+) and recent studies show that Ag(+) impairs neural cell replication and differentiation in culture, suggesting that in vivo exposures could compromise neurodevelopment. To determine whether Ag(+) impairs development in vivo, we examined the effects of exposure on survival, morphological, and behavioral parameters in zebrafish embryos and larvae. We exposed zebrafish from 0 to 5days post-fertilization to concentrations of Ag(+) ranging from 10nM to 100microM in order to assess effects on survival and early embryonic development. We then tested whether concentrations below the threshold for dysmorphology altered larval behavior and subsequent survival. Ag(+) concentrations >or=3microM significantly reduced embryonic survival, whereas 1microM delayed hatching with no effect on survival. Reducing the concentration to as low as 0.1microM delayed the inflation of the swim bladder without causing gross dysmorphology or affecting hatching. At this concentration, swimming activity was impaired, an effect that persisted past the point where swim bladder inflation became normal; in contrast, general motor function was unaffected. The early behavioral impairment was then predictive of subsequent decreases in survival. Ag(+) is a developmental toxicant at concentrations only slightly above allowable levels. At low concentrations, Ag(+) acts as a neurobehavioral toxicant even in the absence of dysmorphology.
纳米银在消费品和医疗产品中的应用日益广泛，导致人类和环境接触纳米银的几率增加。纳米银通过释放银离子（Ag(+)）来发挥抗菌/抗真菌作用，最近的研究表明，Ag(+)会损害培养中的神经细胞复制和分化，这表明体内暴露可能会损害神经发育。为了确定 Ag(+)是否会损害体内发育，我们研究了暴露于 Ag(+)对斑马鱼胚胎和幼虫的存活、形态和行为参数的影响。我们从受精后 0 到 5 天，将斑马鱼暴露于 10nM 至 100μM 的 Ag(+)浓度中，以评估其对存活和早期胚胎发育的影响。然后，我们测试了低于形态畸形阈值的浓度是否会改变幼虫的行为和随后的存活。Ag(+)浓度≥3μM 显著降低胚胎存活率，而 1μM 延迟孵化，但对存活率没有影响。将浓度降低至低至 0.1μM 可延迟气囊膨胀，但不会导致明显的畸形或影响孵化。在该浓度下，游泳活动受损，这种效应持续到气囊膨胀恢复正常；相比之下，一般运动功能不受影响。早期的行为损伤随后预测了存活率的降低。Ag(+)是一种发育毒物，其浓度仅略高于允许水平。在低浓度下，即使没有形态畸形，Ag(+)也会作为神经行为毒物发挥作用。
