AgNP Exposure Research Articles

Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure

Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs. Commonly regulated genes comprised only about 10 and 20% of all differentially expressed genes in PVP-AgNP and cit-AgNP exposed mice, respectively. Commonly regulated biological processes included glutathione metabolic process and cellular oxidant detoxification. Commonly regulated pathways included Keap-Nrf2, PPAR, MAPK and IL-6 signaling pathways. The coding-non-coding gene co-expression analysis revealed that protein-coding genes were co-expressed with a variable number of lncRNAs ranging from one to twenty three and may share functional roles with the protein-coding genes. PVP-AgNP exposure induced a more robust transcriptional response than cit-AgNP exposure characterized by more than two-fold higher number of differentially expressed both protein-coding and lncRNA genes. Our data demonstrate that the surface coating strongly modulates the spectrum and the number of differentially expressed genes after oral AgNP exposure. On the other hand, our data suggest that AgNP exposure can alter drug and chemical sensitivity, metabolic homeostasis and cancer risk irrespective of the coating type, warranting further investigations.

The possible Protective role of alpha-lipoic acid on nanosilver particle-induced hepatotoxicity in male rats

Objective: This study aimed to explore the hepatotoxicity induced by silver nanoparticles (AgNPs) and to assess the hepatoprotective effects of α-lipoic acid (LA) against this toxicity. Methods: Thirty adult male rats were enrolled into 3 equal groups; Control, AgNPs (50 mg/kg/i.P) and LA (100 mg/kg/orally) +AgNPs. After 30 days, blood and liver tissues were collected for further studies. Results: AgNPs exposure enhanced lipid peroxidation(+281.7%) along with declines in glutathione (−58.3%) Level in hepatic tissues. The apparent hepatic oxidative damage was associated with obvious hepatic dysfunction that was ascertained by hepatopathological lesions.As, following AgNPs exposure, hepatic silver content and serum ALT, AST and ALP activities were increased, moreover allows calcium influx and induces intracellular calcium overload. Hepatic tissues treated with AgNPs showed down-regulation of all the genes considered (PGC-1α, Tfam and Nrf2).LA improved the serious effects of AgNPs on the liver tissues through its antioxidant andmetal chelator efficacy. Conclusion: Silver nanoparticles (AgNPs) can induce hepatotoxicity along with oxidative stress, substantial decrease in cell viability with concomitant increases in DNA damage. Oral treatment with LA effectively counteracted the adverse effects of AgNPs.

Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation.

Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, due to their antibacterial properties. AgNPs are also being explored for the treatment of cancer in particular in combination with ionizing radiation. In this work, we studied the effects of AgNPs and ionizing radiation on mitochondrial redox state and function in a panel of lung cell lines (A549, BEAS-2B, Calu-1 and NCI-H358). The exposure to AgNPs caused cell cycle arrest and decreased cell proliferation in A549, BEAS-2B and Calu-1, but not in NCI-H358. The mitochondrial reactive oxygen species (ROS) and protein oxidation increased in a time- and dose-dependent manner in the more sensitive cell lines with the AgNP exposure, but not in NCI-H358. While ionizing radiation also induced changes in the mitochondrial redox profiles, in general, these were not synergistic with the effects of AgNPs with the exception of NCI-H358 and only at a higher dose of radiation.

Functional Autophagic Flux Regulates AgNP Uptake And The Internalized Nanoparticles Determine Tumor Cell Fate By Temporally Regulating Flux.

BackgroundSilver nanoparticles (AgNPs) are known to induce the conserved, cellular, homeostatic process- autophagy in tumor cells. Previous studies primarily focus on the pro-survival role of autophagy post AgNP exposure in tumor cells, but seldom on its role in AgNP uptake, or on the functional significance of autophagy temporal dynamics. Our study sheds more light on the extensive crosstalk that exists between AgNP and autophagy, which can be critical to the improvement of AgNP-induced therapeutic effects.Methodsβ-cyclodextrin (β-CD) coated AgNPs of two different sizes were synthesized by nucleation method and characterized by transmission electron microscopy. Fluorescence microscopy and flow cytometry were used to probe intracellular uptake of AgNPs. Endocytic mechanism of AgNPs was classically analyzed through use of various endocytosis inhibitors. Autophagy was evaluated by immunoblot and fluorescence microscopy. Additionally, immunoblot was performed to monitor Janus Kinase (JNK) signalling, ubiquitination of proteins, expression of endo-lysosomal and apoptotic markers in correlation to AgNP-induced autophagy.ResultsThe intra-cellular route of entry for the small NPs (~9 nm; ss-AgNPs) was different than the large NPs (~19 nm; ls-AgNPs) studied. However, irrespective of their unique route of entry an inhibition of autophagic flux by chloroquine (CQ) reduced uptake of both the AgNPs. In contrary, rapamycin (Rapa), an autophagy inducer enhanced it. Importantly, JNK activation was required for autophagy induction and AgNP uptake. Furthermore, effect of AgNPs on autophagy showed temporal dependency. An enhanced autophagic flux was noted at early time points; however, prolonged exposure resulted in inhibition of flux marked by increase in Rab7, LC3B-II and p62 proteins. Inhibition of flux was associated with lysosomal dysfunction, decreased LAMP1 expression and an increased accumulation of ubiquitinated (Ub) proteins. This resulted in heightened reactive oxygen species (ROS) and consequent cytotoxicity.ConclusionIn this study, we observed that a functional autophagic flux aids AgNP uptake, but AgNPs in turn, overtime, inhibits flux and endo-lysosomal function. We provide critical, novel insights into crosstalk between AgNP and autophagy which can be vital to future AgNP-based therapy development.

Reactivity and Chemical Sintering of Carey Lea Silver Nanoparticles.

Carey Lea silver hydrosol is a rare example of very concentrated colloidal solutions produced with citrate as only protective ligands, and prospective for a wide range of applications, whose properties have been insufficiently studied up to now. Herein, the reactivity of the immobilized silver nanoparticles toward oxidation, sulfidation, and sintering upon their interaction with hydrogen peroxide, sulfide ions, and chlorocomplexes of Au(III), Pd(II), and Pt(IV) was investigated using SEM and X-ray photoelectron spectroscopy (XPS). The reactions decreased the number of carboxylic groups of the citrate-derived capping and promoted coalescence of 7 nm Ag NPs into about 40 nm ones, excluding the interaction with hydrogen peroxide. The increased nanoparticles form loose submicrometer aggregates in the case of sulfide treatment, raspberry-like micrometer porous particles in the media containing Pd(II) chloride, and densely sintered particles in the reaction with inert H2PtCl6 complexes, probably via the formation of surface Ag-Pt alloys. The exposure of Ag NPs to HAuCl4 solution produced compact Ag films along with nanocrystals of Au metal and minor Ag and AgCl. The results are promising for chemical ambient temperature sintering and rendering silver-based nanomaterials, for example, for flexible electronics, catalysis, and other applications.

Both silver ions and silver nanoparticles facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes

Antibiotic resistance in bacteria is a growing threat to global human health. Horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) is recognized as the primary contributor to antibiotic resistance dissemination. Silver nanoparticles (AgNPs) are widely used in personal care products as antimicrobial agents. While heavy metals are known to induce antibiotic resistance in bacteria, it is not known whether AgNPs in the environment can stimulate the HGT of ARGs. Here, we report that both AgNPs and ionic silver Ag+, at environmentally relevant and sub-lethal concentrations, facilitate the conjugative transfer of plasmid-borne ARGs across bacterial genera (from the donor Escherichia coli K-12 LE392 to the recipient Pseudomonas putida KT2440). The underlying mechanisms of the Ag+- or AgNPs-promoted HGT were unveiled by detecting oxidative stress and cell membrane permeability, combined with genome-wide RNA sequencing and proteomic analyses. It was found that both Ag+ and AgNPs exposure induced various bacterial responses that included reactive oxygen species (ROS) generation, membrane damage and the SOS response. This study exposes the potential ecological risks of environmental levels of AgNPs and Ag+ for promoting the spread of ARGs and highlights concerns regarding the management of nanoparticles and heavy metals.

Silver nanoparticles modulate mitochondrial dynamics and biogenesis in HepG2 cells

Silver nanoparticles (AgNPs) are inevitably released into the environment owing to their widespread applications in industry and medicine. The potential of their toxicity has aroused a great concern. Previous studies have shown that AgNPs exposure in HepG2 cells is primarily related to the damage of mitochondria, which includes induction of mitochondrial swelling and increase of intracellular levels of reactive oxygen species (ROS), the collapse of mitochondrial membrane potential and induction of apoptosis through a mitochondrial pathway. In this study, the effects of AgNPs exposure in HepG2 cells on mitochondrial dynamics and biogenesis were investigated. AgNPs were found to induce mitochondrial morphological and structural alterations. The expressions of key proteins (Drp1, Fis1, OPA1, Mff, Mfn1, and Mfn2) related to mitochondrial fission/fusion event were changed. Especially the expression of fission-related protein 1 (p-Drp1) (Ser616) was significantly up-regulated, whereas the expression of mitochondrial biogenesis protein (PGC-1α) was reduced in AgNP-treated cells. Concomitantly, the expression of autophagy marker proteins (LC3B and p62) was increased. The results suggested that AgNPs could trigger cytotoxicity by targeting the mitochondria, resulting in the disruption of mitochondrial function, damage to the mitochondrial structure and morphology, interfering in mitochondrial dynamics and biogenesis. The mitochondria could be a critical target of AgNPs in cells. The functions of mitochondria could be used for assessing the cytotoxic effects associated with AgNPs in cells.

Phytotoxic effect of silver nanoparticles on seed germination and growth of terrestrial plants

Silver nanoparticles (AgNP) exhibit size and concentration dependent toxicity to terrestrial plants, especially crops. AgNP exposure could decrease seed germination, inhibit seedling growth, affect mass and length of roots and shoots. The phytotoxic pathway has been partly understood. Silver (as element, ion or AgNP) accumulates in roots/leaves and triggers the defense mechanism at cellular and tissue levels, which alters metabolism, antioxidant activities and related proteomic expression. Botanical changes (either increase or decrease) in response to AgNP exposure include reactive oxygen species generation, superoxide dismutase activities, H2O2 level, total chlorophyll, proline, carotenoid, ascorbate and glutathione contents, etc. Such processes lead to abnormal morphological changes, suppression of photosynthesis and/or transpiration, and other symptoms. Although neutral or beneficial effects are also reported depending on plant species, adverse effects dominate in majority of the studies. More in depth research is needed to confidently draw any conclusions and to guide legislation and regulations.

The Effects of Genotype × Phenotype Interactions on Transcriptional Response to Silver Nanoparticle Toxicity in Organotypic Cultures of Murine Tracheal Epithelial Cells.

The airway epithelium is critical for maintaining innate and adaptive immune responses, and occupational exposures that disrupt its immune homeostasis may initiate and amplify airway inflammation. In our previous study, we demonstrated that silver nanoparticles (AgNP), which are engineered nanomaterials used in multiple applications but primarily in the manufacturing of many antimicrobial products, induce toxicity in organotypic cultures derived from murine tracheal epithelial cells (MTEC), and those differentiated toward a "Type 2 [T2]-Skewed" phenotype experienced an increased sensitivity to AgNP toxicity, suggesting that asthmatics could be a sensitive population to AgNP exposures in occupational settings. However, the mechanistic basis for this genotype × phenotype (G × P) interaction has yet to be defined. In this study, we conducted transcriptional profiling using RNA-sequencing to predict the enrichment of specific canonical pathways and upstream transcriptional regulators to assist in defining a mechanistic basis for G × P effects on AgNP toxicity. Organotypic cultures were derived from MTEC across 2 genetically inbred mouse strains (A/J and C57BL/6J mice), 2 phenotypes ("Normal" and "T2-Skewed"), and 1 AgNP exposure (an acute 24 h exposure) to characterize G × P effects on transcriptional response to AgNP toxicity. The "T2-Skewed" phenotype was marked by increased pro-inflammatory T17 responses to AgNP toxicity, which are significant predictors of neutrophilic/difficult-to-control asthma and suggests that asthmatics could be a sensitive population to AgNP exposures in occupational settings. This study highlights the importance of considering G × P effects when identifying these sensitive populations, whose underlying genetics or diseases could directly modify their response to AgNP exposures.

Biocompatible green synthesized silver nanoparticles impact on insecticides resistant developing enzymes of dengue transmitted mosquito vector

The growing interest in nanomaterial-based products in various fields urged to study the influence of different nano-products on the ecosystem and on various insect pests. In this study, we evaluated insecticides resistant influenced important biochemical constituents of A. aegypti upon the exposure of green synthesized A. reticulata silver nanoparticle (Ar–AgNPs) for 24 h at their lethal threshold concentration. The AgNPs exposed and control mosquito larval homogenates of the protein content, acetylcholinesterase, specific detoxification enzymes α- and β-carboxylesterase and other anti-oxidant or effective insecticides resistant developed enzyme named glutathione S-transferase (GST) were studied. The larvicidal activity of AgNPs at their lethal threshold concentration (4.5 µg/ml) were monitored for 12 and 24 h and prompted time dependent mortality rate were 23.3 ± 0.57 and 46.6 ± 0.57% respectively. Further, the biochemical constituents of protein content of AgNPs exposed larval homogenates were quantitatively higher compared to the control, but, in the qualitative analysis of separated protein in the electrophoresed gel revealed, the expression protein was down regulated. The important esterase enzymes of acetylcholinesterase, α-and β-carboxylesterase and GST enzymes were significantly reduced upon the exposure of AgNPs compared to the control larval body homogenates respectively. In the qualitative analysis, isoenzyme of β-carboxylesterase expression level was also down regulated. Followed by these investigations, it is clearly showed that A. reticulata mediated synthesized AgNPs have the potent deleterious impact on fourth instar larvae of A. aegypti physiological system by inhibiting important esterase enzyme groups.

Silver Nanoparticles Addition in Poly(Methyl Methacrylate) Dental Matrix: Topographic and Antimycotic Studies.

The widespread use of nanoparticles (NPs) in medical devices has opened a new scenario in the treatment and prevention of many diseases and infections owing to unique physico-chemical properties of NPs. In this way, silver nanoparticles (AgNPs) are known to have a strong antimicrobial activity, even at low concentrations, due to their ability to selectively destroy cellular membranes. In particular, in the field of dental medicine, the use of AgNPs in different kinds of dental prosthesis matrixes could be a fundamental tool in immunodepressed patients that suffer of different oral infections. Candida albicans (C. albicans), an opportunistic pathogenic yeast with high colonization ability, is one of the causative agents of oral cavity infection. In our work, we added monodispersed citrate-capping AgNPs with a size of 20 nm at two concentrations (3 wt% and 3.5 wt%) in poly(methyl methacrylate) (PMMA), the common resin used to develop dental prostheses. After AgNPs characterization, we evaluated the topographical modification of PMMA and PMMA with the addition of AgNPs by means of atomic force microscopy (AFM), showing the reduction of surface roughness. The C. albicans colonization on PMMA surfaces was assessed by the Miles and Misra technique as well as by scanning electron microscopy (SEM) at 24 h and 48 h with encouraging results on the reduction of yeast viability after AgNPs exposure.

Bio-Inspired Silver Nanoparticles Impose Metabolic and Epigenetic Toxicity to Saccharomyces cerevisiae.

Silver nanoparticles (AgNPs) have many applications in various fields, including biomedical applications. Due to the broad range of applications, they are considered as the leading fraction of manufactured nanoparticles. AgNPs are synthesized by different types of chemical and biological (green) methods. Previously, biologically synthesized AgNPs were considered safe for the environment and humans. However, new toxicity evidence have initiated a more careful assessment to delineate the toxicity mechanisms associated with these nanoparticles. This study demonstrates the use of aqueous gooseberry extract for AgNP preparation in a time- and cost-effective way. Ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, and dynamic light scattering confirm the formation of AgNPs, with an average size between 50 and 100 nm. Untargeted 1H-nuclear magnetic resonance-based metabolomics revealed manyfold up- and down-regulation in the concentration of 55 different classes of annotated metabolites in AgNP-exposed yeast Saccharomyces cerevisiae cells. Based on their chemical nature and cellular functions, these metabolites are classified into amino acids, glycolysis and the tricarboxylic acid (TCA) cycle, organic acids, nucleotide metabolism, urea cycle, and lipid metabolism. Transcriptome analysis revealed that the genes involved in oxidative stress mitigation maintain their expression levels, whereas the genes of the TCA cycle and lipid metabolism show drastic down-regulation upon AgNP exposure. Moreover, they can induce alteration in histone epigenetic marks by altering the methylation and acetylation of selected histone H3 and H4 proteins. Altogether, we conclude that the selected dose of biologically synthesized AgNPs impose toxicity by modulating the transcriptome, epigenome, and metabolome of eukaryotic cells, which eventually cause disequilibrium in cellular metabolism leading to toxicity.

Intracellular Dissolution of Silver Nanoparticles: Evidence from Double Stable Isotope Tracing.

To track transformations of silver nanoparticles (AgNPs) in vivo, HepG2 and A549 cells were cocultured with two enriched stable Ag isotopes (107AgNPs and 109AgNO3) at nontoxic doses. After enzymatic digestion, 107AgNPs, ionic 107Ag+ and 109Ag+ in exposed cells could be separated and quantified by liquid chromatography combined with ICP-MS. We found that ratios of 107Ag+ to total 107Ag and proportions of 107Ag+/ 109Ag+ in cells increased gradually after exposure, proving that the Trojan-horse mechanism occurred, i.e., AgNPs released high contents of Ag+ after internalization. While the presence of 109Ag+ (5 and 100 μg/L) has little influence on the uptake of 107AgNPs (0.1 and 2 mg/L), the presence of 107AgNPs at a high dose (2 mg/L) dramatically increases the ingestion of 109Ag+, even though 107AgNPs at a low dose (100 μg/L) showed negligible effects on the internalization of 109Ag+. Cellular homeostasis may be perturbed under sublethal exposure of 107AgNPs, and thus enhanced uptake of 109Ag+. Our findings suggest that the widely adopted control experiments in toxicology studies, culturing organisms with AgNO3 at the same concentration of Ag+ in the AgNP exposure medium, may underestimate uptake of Ag+ and thus cannot exclude suspected toxic effects of Ag+ at high AgNP exposure doses.

Silver nanoparticles alter epithelial basement membrane integrity, cell adhesion molecule expression, and TGF-β1 secretion

Silver nanoparticles (AgNPs) are widely used in consumer and pharmaceutical products due to their antipathogenic properties. However, safety concerns have been raised due to their bioactive properties. While reports have demonstrated AgNPs can embed within the extracellular matrix, their effects on basement membrane (BM) production, integrin engagement, and tissue-integrity are not well-defined. This study analyzed the effects of AgNPs on BM production, composition and integrin/focal adhesion interactions in representative lung, esophageal, breast and colorectal epithelia models. A multidisciplinary approach including focused proteomics, QPCR arrays, pathway analyses, and immune-based, structural and functional assays was used to identify molecular and physiological changes in cell adhesions and the BM induced by acute and chronic AgNP exposure. Dysregulated targets included CD44 and transforming growth factor-beta, two proteins frequently altered during pathogenesis. Results indicate AgNP exposure interferes with BM and cell adhesion dynamics, and provide insight into the mechanisms of AgNP-induced disruption of epithelial physiology.

Ginkgo biloba mitigates silver nanoparticles-induced hepatotoxicity in Wistar rats via improvement of mitochondrial biogenesis and antioxidant status.

Silver nanoparticles (AgNPs) are noble metal nanoparticles, due to their good physicochemical properties, which have been exploited in biological applications. Nanotechnological applications advance very quickly while few literatures assessed the effects of natural products on the risks of nanoparticles in vivo. Thirty male adult rats were enrolled equally into: control, AgNPs (50mg/kg b.w i.p 3 times/week) and GBE (100mg/kg b.w daily per os)+AgNPs. After 30days, the assessment of liver function, antioxidative status, mitochondrial biogenesis, and histopathological analyses were performed. AgNP exposure enhanced thehepatic lipid peroxidation (+ 281.7%) along with a decline in the reducedglutathione (- 58.3%) levels. The apparent hepatic oxidative damage was associated with obvious hepatic dysfunction that was ascertained by alteration of serum liver enzymatic biomarkers, lipid profile, and pathological hepatic lesions. Following AgNP exposure, hepatic silver and calcium contents were increased without changes in the trace element concentrations. Finally, the mRNA transcripts of hepatic PGC-1α, mtTFA, and Nrf2 weredownregulated after AgNP exposure. Interestingly, GBE has the ability to alleviate AgNP-induced hepatic damage assessed by augmentation of reducedglutathione level and mitochondrial biogenesis. This study explored the potential protective role of GBE on AgNPs-induced hepatotoxicity via attenuation of oxidative stress, substantial enhancement of cell viability with concomitant mitigating DNA damage, and mitochondrial dysfunction.

Abstract 887: Silver nanoparticles and ionizing radiation induce mitochondrial protein oxidation and effects on cell cycle and proliferation in lung cancer cell lines

Abstract Silver nanoparticles (AgNP) are widely applied nanomaterials for both commercial and clinical biomedical applications. AgNP have been shown to have cytotoxicity in various cancer cell lines, as well as radiosensitizing properties. The AgNPs may induce free radicals via Fenton-type reactions, but the cellular mechanisms related to reactive oxygen species (ROS) production remain largely unknown. Both ionizing radiation (IR) and AgNP exposure lead to apoptotic and necrotic cell death through mechanisms that involve DNA damage and induction of oxidative stress, possibly targeting mitochondria. Changes in the thiol redox state of mitochondrial proteins, such as protein sulfenylation, play an important role in a number of cellular processes, and mitochondrial damage and dysfunction along with increased mitochondrial ROS are implicated in a range of human diseases such as cancer. In this work we studied the molecular effects of AgNP exposure with and without IR in a panel of lung cell lines (three cancer cell lines: A549, Calu-1 and NCI-H358 and one immortalized lung epithelial cell line: BEAS-2B). Both AgNP and IR exposures increased mitochondrial protein oxidation detected by a recently developed mitochondria targeted probe for protein sulfenylation (DCP-NEt2C). This increase in DCP-NEt2C labeling was dose and time dependent and the exposures also showed a combined effect. Moreover, the exposures induced changes in cell cycle and decreased cellular proliferation. There were marked differences between different cell lines, likely reflecting differences in the cellular redox state and metabolism. In conclusion, the AgNP and IR exposures increase the mitochondrial ROS as demonstrated by increased protein oxidation and have effects on the cell cycle and cell proliferation. They also appear to have a combined effect which might have implications for clinical applications as well as environmental risk assessment. Citation Format: Reetta J. Holmila, Stephen A. Vance, Ravi Singh, S. Bruce King, Cristina M. Furdui. Silver nanoparticles and ionizing radiation induce mitochondrial protein oxidation and effects on cell cycle and proliferation in lung cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 887.

Molecular and Morphological Evidence of Hepatotoxicity after Silver Nanoparticle Exposure: A Systematic Review, In Silico, and Ultrastructure Investigation

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

Muted responses to Ag accumulation by plankton to chronic and pulse exposure to silver nanoparticles in a boreal lake

Silver nanoparticles (AgNPs) are an emerging class of contaminants with the potential to impact ecosystem structure and function. AgNPs are antimicrobial, suggesting that microbe-driven ecosystem functions may be particularly vulnerable to AgNP exposure. Predicting the environmental impacts of AgNPs requires in situ investigation of environmentally relevant dosing regimens over time scales that allow for ecosystem-level responses. We used 3000 L enclosures installed in a boreal lake to expose plankton communities to chronic and pulse AgNP dosing regimens with concentrations mimicking those recorded in natural waters. We compared temporal patterns of plankton responses, Ag accumulation, and ecosystem metabolism (i.e., daily ecosystem respiration, gross primary production, and net ecosystem production) for 6 weeks of chronic dosing and 3 weeks following a pulsed dose. Ag accumulated in microplankton and zooplankton, but carbon-specific Ag was nonlinear over time and generally did not predict plankton response. Ecosystem metabolism did not respond to either AgNP exposure type. This lack of response corresponded with weak microplankton responses in the chronic treatments but did not reflect the stronger microplankton response in the pulse treatment. Our results suggest that lake ecosystem metabolism is somewhat resistant to environmentally relevant concentrations of AgNPs and that organismal responses do not necessarily predict ecosystem-level responses.

The Effects of Gene × Environment Interactions on Silver Nanoparticle Toxicity in the Respiratory System.

Silver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. AgNP toxicity in the respiratory system is well characterized, but few in vitro or in vivo studies have evaluated the effects of interactions between host genetic and acquired factors or gene × environment interactions (G × E) on AgNP toxicity in the respiratory system. The primary goal of this article is to review host genetic and acquired factors identified across in vitro and in vivo studies and prioritize those necessary for defining exposure limits to protect all populations. The impact of these exposures and the work being done to address the current limited protections are also discussed. Future research on G × E effects on AgNP toxicity is warranted and will assist with informing regulatory or recommended exposure limits that enforce special protections for all populations to AgNP exposures in occupational settings.

Alteration in the mRNA expression of genes associated with gastrointestinal permeability and ileal TNF-\u03b1 secretion due to the exposure of silver nanoparticles in Sprague\u2013Dawley rats

BackgroundSilver ions from silver nanoparticles (AgNP) or AgNPs themselves itself that are ingested from consumer health care products or indirectly from absorbed food contact material can interact with the gastrointestinal tract (GIT). The permeability of the GIT is strictly regulated to maintain barrier function and proper nutrient absorption. The single layer intestinal epithelium adheres and communicates actively to neighboring cells and the extracellular matrix through different cell junctions. In the current study, we hypothesized that oral exposure to AgNPs may alter the intestinal permeability and expression of genes controlling cell junctions. Changes in cell junction gene expression in the ileum of male and female rats administered different sizes of AgNP for 13-weeks were assessed using qPCR.ResultsThe results of this study indicate that AgNPs have an altering effect on cell junctions that are known to dictate intestinal permeability. mRNA expression of genes representing tight junction (Cldn1, Cldn5, Cldn6, Cldn10 and Pecam1), focal adhesion (Cav1, Cav2, and Itgb2), adherens junction (Pvrl1, Notch1, and Notch2), and hemidesmosome (Dst) groups were upregulated significantly in females treated with 10 nm AgNP, while no change or downregulation of same genes was detected in male animals. In addition, a higher concentration of pro-inflammatory cytokine, TNF-α, was noticed in AgNP-treated female animals as compared to controls.ConclusionsThis study proposes that interaction of silver with GIT could potentially initiate an inflammatory process that could lead to changes in the gastrointestinal permeability and/or nutrient deficiencies in sex-specific manner. Fully understanding the mechanistic consequences of oral AgNP exposure may lead to stricter regulation for the commercial usage of AgNPs and/or improved clinical therapy in the future.