Silver nanoparticles have lethal and sublethal adverse effects on development and longevity by inducing ROS-mediated stress responses

Abstract

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.

Synthesis of non-toxic, biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

“…On the basis of these ndings, it was demonstrated that the concentration range from 10 to 100 mg L À1 of AgNPs-EW did not cause any signicant acute and chronic toxic effects on the reproductive traits, namely the fecundity, hatchability, viability, duration of development, and pigmentation of Drosophila. We compared these ndings with previously reported AgNPs toxicity studies on Drosophila and summarize the results in Table 2, [58][59][60][61][62] which clearly shows that AgNPs toxicity is based on the capping agents used for nanoparticles synthesis, size, and dose. Based on our literature study, we understand that this is the rst report of AgNPs-EW having no acute and chronic toxicity effects on Drosophila at the maximum concentration, which is 100 mg L À1 .…”

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

“…One common form of lysosomal dysfunction that has been associated with nanomaterial treatments is increased lysosomal membrane permeabilization (LMP). Proton pump inhibitors, such as bafilomycin A1, that block autophagic flux predispose cells to LMP, triggering apoptosis through the LMP-induced release of pro-apoptosis mediators such as cathepsin [45]. LMP is a recognized cell death mechanism that can result in mitochondrial membrane permeabilization through several mechanisms, including lysosomal-iron mediated oxidative stress and the release of cathepsin or other lysosomal associated hydrolases [45].…”

“…Proton pump inhibitors, such as bafilomycin A1, that block autophagic flux predispose cells to LMP, triggering apoptosis through the LMP-induced release of pro-apoptosis mediators such as cathepsin [45]. LMP is a recognized cell death mechanism that can result in mitochondrial membrane permeabilization through several mechanisms, including lysosomal-iron mediated oxidative stress and the release of cathepsin or other lysosomal associated hydrolases [45]. As lysosomal dysfunction has been involved in disease pathogenesis, the association of nanoparticle exposure and lysosomal dysfunction may have relevance to nanomaterial-induced toxicity levels, especially chronic toxicity.…”

“…Since lysosomal degradation pathways play vital roles in cellular homeostasis, lysosomal dysfunction has been associated with several diseases, termed lysosomal storage disorders [43,46]. Many types of lysosomal perturbations are also associated with autophagy dysfunction, blocking autophagosomes and lysosome fusion and promoting the accumulation of autophagosomes and other autophagy-related substrates (e.g., ubiquitinated protein aggregates) [45]. Autophagy dysfunction can result from lysosomal overload, which prevents autophagosome-lysosome fusion.…”

Toxic and Genotoxic Effects of Silver Nanoparticles in Drosophila

“…Delays in the development from egg-toadult have been detected when eggs or larvae were exposed (Gorth et al 2011;Philbrook et al 2011;Vecchio et al 2013;Han et al 2014;Vega-Alvarez et al 2014;Raj et al 2017a). Interestingly, these effects were translated to the emerged adults who present shortened life span, mating success decrease, and less fertility (Key et al 2011;Panacek et al 2011;Posgai et al 2011;Armstrong et al 2013;Tian et al 2013;Mao et al 2018). The observed loss of fertility was associated with a decreased number of germline stem cells (Ong et al 2016), and also a reduced pigmentation was observed in adults, mainly depending on AgNPs concentration (Panacek et al 2011;Avalos et al 2015;Phatak et al 2016).…”