Gold Nanoparticles Disrupt Zebrafish Eye Development and Pigmentation
Gold Nanoparticles Disrupt Zebrafish Eye Development and Pigmentation
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DOI：
10.1093/toxsci/kft081
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发表时间：
2013-06-01
影响因子：
3.8
通讯作者：
Tanguay, Robert L.
中科院分区：
文献类型：
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作者：
Kim, Ki-Tae;Zaikova, Tatiana;Tanguay, Robert L.
为了充分了解金纳米颗粒(AuNPs)的潜在危害，还需要进行系统的毒理学研究。由于其生物医学应用正在迅速发展，我们在一个体内胚胎斑马鱼模型上研究了AuNPs的发育毒性，暴露浓度从0.08到50 mg/L。斑马鱼胚胎暴露于1.3 nm的AuNPs(阳离子配体N，N，N-三甲基氨乙硫醇)，导致较小的色素异常。我们确定TMAT-AuNPs导致眼内细胞死亡显著增加，这与P53和Bax基因表达增加有关。在TMAT-AuNPs暴露的胚胎中，调控眼睛发育的关键转录因子(pax6a、pax6b、OTX2和RX1)和色素沉着(Sox10)的表达模式都以浓度依赖的方式被抑制。通过整装原位杂交，观察到pax6a、rx1、sox10和mitfa在胚胎中的空间定位降低。在亚致死浓度的TMAT-AuNPs暴露下，胚胎的游泳行为表现出低活性，胚胎表现出轴突生长抑制。总体而言，这些结果表明，TMAT-AuNPs扰乱了眼睛发育和色素沉着的进程，从而继续损害发育中的斑马鱼的行为和神经元。
Systematic toxicological study is still required to fully understand the hazard potentials of gold nanoparticles (AuNPs). Because their biomedical applications are rapidly evolving, we investigated developmental toxicity of AuNPs in an in vivo embryonic zebrafish model at exposure concentration ranges from 0.08 to 50mg/l. Exposure of zebrafish embryos to 1.3nm AuNPs functionalized with a cationic ligand, N,N,N-trimethylammoniumethanethiol (TMAT-AuNPs), resulted in smaller malpigmented eyes. We determined that TMAT-AuNPs caused a significant increase of cell death in the eye, which was correlated with an increase in gene expression of p53 and bax. Expression patterns of key transcription factors regulating eye development (pax6a, pax6b, otx2, and rx1) and pigmentation (sox10) were both repressed in a concentration-dependent manner in embryos exposed to TMAT-AuNPs. Reduced spatial localization of pax6a, rx1, sox10, and mitfa was observed in embryos by whole-mount in situ hybridization. The swimming behavior of embryos exposed to sublethal concentrations of TMAT-AuNPs showed hypoactivity, and embryos exhibited axonal growth inhibition. Overall, these results demonstrated that TMAT-AuNPs disrupt the progression of eye development and pigmentation that continues to behavioral and neuronal damage in the developing zebrafish.