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Environ Sci Technol,
2015]
The use of antibacterial silver nanomaterials in consumer products ranging from textiles to toys has given rise to concerns over their environmental toxicity. These materials, primarily nanoparticles, have been shown to be toxic to a wide range of organisms; thus methods and materials that reduce their environmental toxicity while retaining their useful antibacterial properties can potentially solve this problem. Here we demonstrate that silver nanocubes display a lower toxicity toward the model plant species Lolium multiflorum while showing similar toxicity toward other environmentally relevant and model organisms (Danio rerio and Caenorhabditis elegans) and bacterial species (Esherichia coli, Bacillus cereus, and Pseudomonas aeruginosa) compared to quasi-spherical silver nanoparticles and silver nanowires. More specifically, in the L. multiflorum experiments, the roots of silver nanocube treated plants were 5.3% shorter than the control, while silver nanoparticle treated plant roots were 39.6% shorter than the control. The findings here could assist in the future development of new antibacterial products that cause less environmental toxicity after their intended use.
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Environ Sci Technol,
2012]
The rapidly increasing use of silver nanoparticles (Ag NPs) in consumer products and medical applications has raised ecological and human health concerns. A key question for addressing these concerns is whether Ag NP toxicity is mechanistically unique to nanoparticulate silver, or if it is a result of the release of silver ions. Furthermore, since Ag NPs are produced in a large variety of monomer sizes and coatings, and since their physicochemical behavior depends on the media composition, it is important to understand how these variables modulate toxicity. We found that a lower ionic strength medium resulted in greater toxicity (measured as growth inhibition) of all tested Ag NPs to Caenorhabditis elegans and that both dissolved silver and coating influenced Ag NP toxicity. We found a linear correlation between Ag NP toxicity and dissolved silver, but no correlation between size and toxicity. We used three independent and complementary approaches to investigate the mechanisms of toxicity of differentially coated and sized Ag NPs: pharmacological (rescue with trolox and N-acetylcysteine), genetic (analysis of metal-sensitive and oxidative stress-sensitive mutants), and physicochemical (including analysis of dissolution of Ag NPs). Oxidative dissolution was limited in our experimental conditions (maximally 15% in 24 h) yet was key to the toxicity of most Ag NPs, highlighting a critical role for dissolved silver complexed with thiols in the toxicity of all tested Ag NPs. Some Ag NPs (typically less soluble due to size or coating) also acted via oxidative stress, an effect specific to nanoparticulate silver. However, in no case studied here was the toxicity of a Ag NP greater than would be predicted by complete dissolution of the same mass of silver as silver ions.
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Environ Toxicol Chem,
2013]
A new toxicity test medium for Caenorhabditis elegans is presented. The test solution is designed to provide a better representation of natural soil pore water conditions than currently available test media. The medium has a composition that can readily be modified to allow for studies of the influences of a range of environmentally relevant parameters on nematode biology and toxicology. Tests conducted in the new medium confirmed that nematodes' reproduction was possible at a range of solution pH levels, offering the potential to conduct toxicity studies under a variety of conditions. A test to establish silver nanoparticle and dissolved silver nitrate toxicity, a study type not feasible in M9 or agar media due to precipitation and nanoparticle agglomeration, indicated lower silver nanoparticle (median effective concentration [EC50] of 6.5mg Ag/L) than silver nitrate (EC50 0.28mg Ag/L) toxicity. Characterization identified stable nanoparticle behavior in the new test medium.
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J Appl Toxicol,
2013]
Studies on the effects of nanomaterial exposure in mammals are limited, and new methods for rapid risk assessment of nanomaterials are urgently required. The utility of Caenorhabditis elegans cultured in axenic liquid media was evaluated as an alternative in vivo model for the purpose of screening nanomaterials for toxic effects. Spherical silver nanoparticles of 10nm diameter (10nmAg) were used as a test material, and ionic silver from silver acetate as a positive control. Silver uptake and localization, larval growth, morphology and DNA damage were utilized as endpoints for toxicity evaluation. Confocal reflection analysis indicated that 10nmAg localized to the lumen and tissues of the digestive tract of C. elegans. 10nmAg at 10gml(-1) reduced the growth of C. elegans larvae, and induced oxidative damage to DNA as measured by 8-OH guanine levels. Consistent with previously published studies using mammalian models, ionic silver suppressed growth in C. elegans larvae to a greater extent than 10nmAg. Our data suggest that medium-throughput growth screening and DNA damage analysis along with morphology assessments in C. elegans could together provide powerful tools for rapid toxicity screening of nanomaterials.
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Chemosphere,
2018]
Silver nanomaterials (AgNMs) of various shapes and sizes are manufactured for different purposes and used as ingredients in a wide variety of products and applications. Recently, the toxicity of AgNMs has attracted significant attention. However, the effect of the shape of AgNMs (particles, wires, plates) on their toxicity in soil ecosystems remains poorly understood. In this study, we added AgNMs of different shapes and sizes (silver nanoparticles, AgNPs; 10m silver nanowires, 10-AgNWs; 20m silver nanowires, 20-AgNWs; silver nanoplates, AgPLs) to natural soil and determined their effect on the growth and reproduction of the free-living nematode, Caenorhabditis elegans. AgNPs and AgPLs were found to inhibit the growth and reproduction of C.elegans, whereas AgNWs had a negligible effect. Among these AgNMs, the results of this study suggest AgNPs are the most toxic. This confirms that the shape of AgNPs plays a significant role in their toxicity level. To the best of our knowledge, this is the first comparative analysis of the shape-dependent toxicity of AgNMs in the soil using nematode C.elegans. This study provides a scientific reference for assessing shape-dependent soil nanotoxicity.
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Toxicol Rep,
2014]
The in vivo toxicity to eukaryotes of nanosilver (AgNP) spheres and plates in two sizes each was assessed using the simple model organism Caenorhabditis elegans. For each shape, smaller AgNP size correlated with higher toxicity, as indicated by reduced larval growth. Smaller size also correlated with significant increases in silver uptake for silver nanospheres. Citrate coated silver spheres of 20 nm diameter induced an innate immune response that increased or held steady over 24 h, while regulation of genes involved in metal metabolism peaked at 4 h and subsequently decreased. For AgNP spheres, coating altered bioactivity, with a toxicity ranking of polyethylene glycol (PEG) > polyvinylpyrrolidone (PVP) branched polyethyleneimine (BPEI) > citrate, but silver uptake ranking of PEG > PVP > citrate > BPEI. Our findings in C. elegans correlate well with findings in rodents for AgNP size vs. uptake and toxicity, as well as for induction of immune effectors, while using methods that are faster and far less expensive, supporting the use of C. elegans as an alternative model for early toxicity screening.
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Biochem Biophys Res Commun,
2017]
The metabolic pathway such as glyoxylate cycle (GC) enables Candida albicans, to survive under glucose deficient conditions prevalent in the hostile niche. Thus its key enzymes (Isocitrate lyase; ICL and malate synthase; MLS) represent attractive targets against C. albicans. We have previously reported the antifungal potential of a natural monoterpenoid perillyl alcohol (PA). The present study uncovers additional role of PA as a potent GC inhibitor. We explored that PA phenocopied ICL1 deletion mutant and were hypersensitive under low carbon utilizing conditions. The effect of PA on GC was substantiated by molecular docking analyses, which reveals the in-silico binding affinity of PA with ICL and MLS and explored that PA binds to the active sites of both proteins with better binding energy in comparison to their known inhibitors 3-nitropropionate and bromopyruvate respectively. Enzyme kinetics by Lineweaver-Burk plot unravels that PA inhibits ICL and MLS enzymes in competitive and non-competitive manner respectively. Moreover, semi-quantitative RT-PCR indicated that PA inhibits ICL1 and MLS1 mRNA expressions. Lastly, we demonstrated the antifungal efficacy of PA by enhanced survival of Caenorhabditis elegans model and less hemolytic activity (29%) on human blood cells. Further studies are warranted for PA to be considered as viable drug candidate.
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Chemistry,
2011]
A simple, sensitive, and highly specific lipid targeting Raman probe (Nile red coated silver nanoparticles) has been developed to image living nematode Caenorhabditis elegans (C. elegans). Our idea of imaging lipids in C. elegans is to combine the specificity of the fluorescent dye, Nile red, and the highly enhanced Raman scattering on the silver nanoparticles. Our strategy involves the fabrication of a lipid targeting probe, which is incorporated into the intracellular intestinal granules of C. elegans by incubating these worms in the solution containing Raman probes, resulting in an uptake and subsequent incorporation of these Raman probes into the intestinal granule, thus allowing fast visualization of lipid droplets through a conventional confocal imaging technique.
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Environ Sci Technol,
2014]
Significant progress has been made in understanding the toxicity of silver nanoparticles (Ag NPs) under carefully controlled laboratory conditions. Natural organic matter (NOM) is omnipresent in complex environmental systems, where it may alter the behavior of nanoparticles in these systems. We exposed the nematode Caenorhabditis elegans to Ag NP suspensions with or without one of two kinds of NOM, Suwannee River and Pony Lake fulvic acids (SRFA and PLFA, respectively). PLFA rescued toxicity more effectively than SRFA. Measurement of total tissue silver content indicated that PLFA reduced total organismal (including digestive tract) uptake of ionic silver, but not of citrate-coated Ag NPs (CIT-Ag NPs). The majority of the CIT-Ag NP uptake was in the digestive tract. Limited tissue uptake was detected by hyperspectral microscopy but not by transmission electron microscopy. Co-exposure to PLFA resulted in the formation of NOM-Ag NP composites (both in medium and in nematodes) and rescued AgNO3- and CIT-Ag NP-induced cellular damage, potentially by decreasing intracellular uptake of CIT-Ag NPs.
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Mar Drugs,
2016]
Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated -3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 M. Dose-dependent treatments with 10-100 M DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%-98.8%. Similarly, dose-dependent treatments with 10-20 M AST reversed the PA toxicity at its IC50 dose and raised these cells' survival to 61.7%-70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity.