Toxicogenomic Responses of Nanotoxicity in Daphnia magna Exposed to Silver Nitrate and Coated Silver Nanoparticles
Ontology highlight
ABSTRACT: Applications for silver nanomaterials in consumer products are rapidly expanding, creating an urgent need for toxicological examination of the exposure potential and ecological effects of silver nanoparticles (AgNPs). The integration of genomic techniques into environmental toxicology has presented new avenues to develop exposure biomarkers and investigate the mode of toxicity of novel chemicals. In the present study we used a 15k oligonucleotide microarray for Daphnia magna, a freshwater crustacean and common indicator species for toxicity, to differentiate between particle specific and ionic silver toxicity and to develop exposure biomarkers for citrate-coated and PVP-coated AgNPs. Gene expression profiles revealed that AgNO3 and AgNPs have distinct expression profiles suggesting different modes of toxicity. However, the gene expression profiles of the different coated AgNPs were similar revealing similarities in the cellular effects of these two particles. Major biological processes disrupted by the AgNPs include protein metabolism and signal transduction. In contrast, AgNO3 caused a downregulation of developmental processes, particularly in sensory development. Metal responsive and DNA damage repair genes were induced by the PVP AgNPs, but not the other treatments. In addition, two specific biomarkers were developed for the environmental detection of PVP AgNPs; although further verification under different environmental conditions is needed. We exposed Daphnia magna to the 1/10 LC50 and LC25 of citrate coated and PVP-coated Ag nanoparticles and Ag+ as AgNO3 for 24-h. For each exposure condition, we performed 6 replicate exposures with 5 individuals in each. All exposures were compared to a unexposed laboratory control.
Project description:Applications for silver nanomaterials in consumer products are rapidly expanding, creating an urgent need for toxicological examination of the exposure potential and ecological effects of silver nanoparticles (AgNPs). The integration of genomic techniques into environmental toxicology has presented new avenues to develop exposure biomarkers and investigate the mode of toxicity of novel chemicals. In the present study we used a 15k oligonucleotide microarray for Daphnia magna, a freshwater crustacean and common indicator species for toxicity, to differentiate between particle specific and ionic silver toxicity and to develop exposure biomarkers for citrate-coated and PVP-coated AgNPs. Gene expression profiles revealed that AgNO3 and AgNPs have distinct expression profiles suggesting different modes of toxicity. However, the gene expression profiles of the different coated AgNPs were similar revealing similarities in the cellular effects of these two particles. Major biological processes disrupted by the AgNPs include protein metabolism and signal transduction. In contrast, AgNO3 caused a downregulation of developmental processes, particularly in sensory development. Metal responsive and DNA damage repair genes were induced by the PVP AgNPs, but not the other treatments. In addition, two specific biomarkers were developed for the environmental detection of PVP AgNPs; although further verification under different environmental conditions is needed.
Project description:Nanoparticles are compounds of emerging concern with largely unknown risks for human and ecological health. It is crucial to evaluate their potential biological impact to prevent unintended adverse effects on human health and the environment. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. We also tested the feasibility of the fathead minnow as an alternative species to elucidate potential adverse effects on humans. Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs for 96h. Microarray analyses were performed on liver and brain. Functional analysis identified potential toxicity pathways and molecular initiating events (MIEs) that were confirmed with functional assays. Data suggested that AgNO3 and PVP-AgNPs had both common and distinct transcriptional effects. The nanoparticles were linked to neurotoxicity and oxidative stress, and identified as a dopamine receptor antagonist. Silver nitrate was also identified as a potential neurotoxicant and was confirmed as adrenergic and cannabinoid receptors antagonist. While silver nitrate and PVP-AgNPs were both potential neurotoxicants, they appeared to act through different MIEs. Fathead minnow is a promising alternative species to elucidate potential adverse effects of relevance to human health. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. FHM were obtained from Aquatic Biosystems (Fort Collins, CO), held in aerated dechlorinated tap water and fed three times daily with Zeigler® AquaTox Feed Gardners, PA, USA). Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs (Luna Innovations, Blackburn, VA) for 96h at 24°C ± 1 with a 90% water change at 48 hours. Microarray analyses were performed on liver and brain.
Project description:Nanoparticles are compounds of emerging concern with largely unknown risks for human and ecological health. It is crucial to evaluate their potential biological impact to prevent unintended adverse effects on human health and the environment. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. We also tested the feasibility of the fathead minnow as an alternative species to elucidate potential adverse effects on humans. Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs for 96h. Microarray analyses were performed on liver and brain. Functional analysis identified potential toxicity pathways and molecular initiating events (MIEs) that were confirmed with functional assays. Data suggested that AgNO3 and PVP-AgNPs had both common and distinct transcriptional effects. The nanoparticles were linked to neurotoxicity and oxidative stress, and identified as a dopamine receptor antagonist. Silver nitrate was also identified as a potential neurotoxicant and was confirmed as adrenergic and cannabinoid receptors antagonist. While silver nitrate and PVP-AgNPs were both potential neurotoxicants, they appeared to act through different MIEs. Fathead minnow is a promising alternative species to elucidate potential adverse effects of relevance to human health.
Project description:Silver exposure is toxic to fish due to disturbances of normal gill function. A proposed toxicity mechanism of silver nanoparticles (AgNP) is derived from the release of silver ions, similar to silver nitrate (AgNO3). However, some datasets support the fact that AgNP can have unique toxic effects that are mediated at the gill. To determine if differences between AgNO3 and AgNP toxicities exist, fathead minnows were exposed to 20 nm PVP- or citrate-coated silver nanoparticles (PVP-AgNP; citrate-AgNP) at the nominal concentration of 200 μg/L or AgNO3 at nominal 6 μg/L for 96 hr. This nominal concentration was applied to approximate the dissolved fraction of Ag in the AgNP suspensions. Mucus production in the water was measured. While mucus production was initially significantly increased in the first 4 h of exposure in all silver treatments compared to control, a decrease in mucus production was observed following 24-96 h of exposure. To determine which genes/pathways are driving this shift in mucus production, gills were dissected and microarray analysis was performed. Hierarchal clustering of differentially expressed genes revealed that all samples distinctly clustered by treatment. There were 109 differentially expressed genes shared among all Ag treatments compared to controls. However, there were 185, 423, and 615 differentially expressed genes unique to AgNO3, PVP-AgNP, and citrate-AgNP, relative to control. While functional analysis indicated several common enriched pathways, such as aryl hydrocarbon receptor signaling, this analysis also indicated some unique pathways between nanosilver and AgNO3. Our results show that AgNO3, PVP-AgNP, and citrate-AgNP exposure affected mucus production in fish gills and also lead to common and unique transcriptional changes.
Project description:Custom D. magna gene expression microarray (Design ID: 023710, Agilent Technologies)were used to characterise gene expression profiles of Daphnia magna neoantes exposed to silver nanoparticles ( AgNPs ) or silver nitrate ( AgNO3 ) for 24 hours.
Project description:We used microarrays to determine transcptional responses to silver nanoparticles (AgNPs) in the mouse liver following oral ingestion. Liver is a major target organ for AgNP accumulation after oral or intravenous exposure. Given that physicochemical properties of AgNPs such as surface coating may influence transcriptional responses to exposure, we evaluated AgNPs with two different surface coatings such as citrate (cit) and polyvinylpirrolidone (PVP). We identified common and unique mRNA and lncRNA expression profiles for cit-AgNPs and PVP-AgNPs. PVP-AgNPs induced a more robust transctiptional response characterized by a 2-fold higher number of differentially expressed mRNAs and lncRNAs.
Project description:Understanding the mode of action of nanomaterials (NMs) aids in improving predictions and environmental risk assessment. In the present study, a high-throughput (HTP) microarray was used to study Enchytraeus crypticus gene expression. Four Ag materials (Ag NM300K, PVP-coated AgNPs, AgNPs, and AgNO3) were tested at reproduction effect concentrations, EC20 and EC50, to anchor gene expression responses to higher effect level. The results showed that while PVP-AgNPs and AgNPs had similar responses, Ag NM300K caused effects via a differentiated transcriptomic profile, with uniquely affected processes (e.g. transcytosis). For the AgNPs, the EC50 negatively affected apoptosis, which can lead to accumulation of abnormal cells and cause apical damage (reproduction). Mechanisms which are known to be related to Ag toxicity and which were observed here for the various Ag forms included apoptosis regulation, cell redox homeostasis, impairment of energy production and response to DNA damage. This HTP genomic tool enabled discrimination between Ag materials, which is not possible via standard tests (i.e. survival and reproduction endpoints). Moreover, gene expression analysis provided information regarding the mechanisms of toxicity of NMs and the pathways uniquely affected by NMs. An adverse outcome pathway (AOP) was drafted for the first time for Ag NMs; this AOP can and should be used as a basis for further research.
Project description:RNA-Seq analysis was used for deep sequencing of transcriptome to detected molecular mechanisms of silver nanoparticles (AgNPs) and distinguish the effects of Arabidopsis thaliana exposure to AgNPs and Ag+.We identified 626 and 767 differentially expressed genes (DEGs) influenced by AgNPs and Ag+ respectively.302 genes were specifically regulated by the AgNPs treatment indicates that the nanoparticle-specific effects.This study provide a valuable resource for the discovery of genes related to special toxicity mechanism of AgNPs.
Project description:In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress.In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. The DEGs were significantly enriched in macropinocytosis and phagocytic vesicles suggesting that the uptake of AgNPs may be mediated by endocytic pathways, while the differential expression of ABC transporters and copper-transporting ATPase implicates active efflux transport of Ag. Several DNA repair pathways were also significantly enriched with differentially expressed cell cycle control genes implying that exposure to AgNPs might have caused DNA damage and G2/M cell cycle arrest. The damage might have resulted from increased ROS production, as evidenced by elevated expression of several antioxidants genes to combat oxidative stress. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress. Integrated analysis of the microRNA and mRNA expression profiles found that the differentially expressed microRNAs target a series of genes involved in many important biological processes, suggesting that E. vannus exposure elicited a broad post-transcriptional regulatory mechanism through microRNAs–mRNAs–biological functions network to cope with the toxicity of AgNPs.
Project description:In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress.In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. The present study conducted transcriptome and microRNAome sequencing for Euplotes vannus to understand the molecular mechanisms by which this protist copes with AgNPs exposure. By transcriptome profiling, 1884 and 5834 differentially expressed genes (DEGs) were identified after one hour and 12 hours exposure to 15 mg/L AgNPs, respectively. The DEGs were significantly enriched in macropinocytosis and phagocytic vesicles suggesting that the uptake of AgNPs may be mediated by endocytic pathways, while the differential expression of ABC transporters and copper-transporting ATPase implicates active efflux transport of Ag. Several DNA repair pathways were also significantly enriched with differentially expressed cell cycle control genes implying that exposure to AgNPs might have caused DNA damage and G2/M cell cycle arrest. The damage might have resulted from increased ROS production, as evidenced by elevated expression of several antioxidants genes to combat oxidative stress. From microRNAsome profiling, totally 16 differentially expressed microRNAs were identified under AgNPs stress. Integrated analysis of the microRNA and mRNA expression profiles found that the differentially expressed microRNAs target a series of genes involved in many important biological processes, suggesting that E. vannus exposure elicited a broad post-transcriptional regulatory mechanism through microRNAs–mRNAs–biological functions network to cope with the toxicity of AgNPs.