Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, Taiwan.
Department of Physiology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City, Taiwan.
Sci Rep. 2018 Feb 5;8(1):2445. doi: 10.1038/s41598-018-20728-z.
Silver nanoparticles (AgNPs) are widely used in the household, medical and industrial sectors due to their effective bactericidal activities and unique plasmonic properties. Despite the promising advantages, safety concerns have been raised over the usage of AgNPs because they pose potential hazards. However, the mechanistic basis behind AgNPs toxicity, particularly the sublethal effects at the organismal level, has remained unclear. In this study, we used a powerful in vivo platform Drosophila melanogaster to explore a wide spectrum of adverse effects exerted by dietary AgNPs at the organismal, cellular and molecular levels. Lethal doses of dietary AgNPs caused developmental delays and profound lethality in developing animals and young adults. In contrast, exposure to sublethal doses, while not deadly to developing animals, shortened the adult lifespan and compromised their tolerance to oxidative stress. Importantly, AgNPs mechanistically resulted in tissue-wide accumulation of reactive oxygen species (ROS) and activated the Nrf2-dependent antioxidant pathway, as demonstrated by an Nrf2 activity reporter in vivo. Finally, dietary AgNPs caused a variety of ROS-mediated stress responses, including apoptosis, DNA damage, and autophagy. Altogether, our study suggests that lethal and sublethal doses of AgNPs, have acute and chronic effects, respectively, on development and longevity by inducing ROS-mediated stress responses.
银纳米粒子（AgNPs）由于其有效的杀菌活性和独特的等离子体特性，广泛应用于家庭、医疗和工业领域。尽管具有广阔的应用前景，但由于 AgNPs 存在潜在危害，其安全性问题引起了人们的关注。然而，AgNPs 毒性的机制基础，特别是在机体水平上的亚致死效应，仍不清楚。在这项研究中，我们使用了强大的体内平台——黑腹果蝇（Drosophila melanogaster）来探索饮食 AgNPs 在机体、细胞和分子水平上产生的广泛不良影响。饮食 AgNPs 的致死剂量会导致发育中的动物和幼体出现发育迟缓及严重的致死现象。相比之下，暴露于亚致死剂量下虽然不会对发育中的动物造成致命影响，但会缩短其成年寿命，并使其对氧化应激的耐受性下降。重要的是，AgNPs 会在组织范围内积累活性氧物种（ROS），并激活 Nrf2 依赖性抗氧化途径，这一点可以通过体内的 Nrf2 活性报告基因得到证实。最后，饮食 AgNPs 会引起多种 ROS 介导的应激反应，包括细胞凋亡、DNA 损伤和自噬。总之，本研究表明，致死和亚致死剂量的 AgNPs 分别通过诱导 ROS 介导的应激反应对发育和寿命产生急性和慢性影响。
