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Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

ABSTRACT: Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress).

SUBMITTER: Mashock MJ

PROVIDER: S-EPMC5135131 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

Mashock Michael J MJ Zanon Tyler T Kappell Anthony D AD Petrella Lisa N LN Andersen Erik C EC Hristova Krassimira R KR

PloS one 20161202 12

Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nan ...[more]

PMID: 27911941

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Project description:Introduction:Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal's organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice. Methods:Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally. Results:TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm-1 and 425 cm-1 in biologically synthesized NPs and between 858 cm-1 and 524 cm-1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs. Conclusion:This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.

Project description:Driven by the need to biosynthesized alternate biomedical agents to prevent and treat infection, copper oxide nanoparticles (CuONPs) have surfaced as a promising avenue. Cyanobacteria-derived synthesis of CuONPs is of substantive interest as it offers an eco-friendly, cost-effective, and biocompatible route. In the present study biosynthesized CuONPs were characterized and investigated regarding their toxicity. Morphological analysis using TEM, SEM and AFM showed the spherical particle size of 20.7 nm with 96% copper that confirmed the purity of CuONPs. Biogenic CuONPs with IC50 value of 64.6 µg ml-1 showed 90% scavenging of free radicals in superoxide radical scavenging assay. CuONPs showed enhanced anti-inflammatory activity by 86% of protein denaturation with IC50 value of 89.9 µg ml-1. Biogenic CuONPs exhibited significant toxicity against bacterial strains with lowest MIC value of 62.5 µg ml-1 for B. cereus and fungal strain with a MIC value of 125 µg ml-1 for C. albicans. In addition CuONPs demonstrated a high degree of synergistic interaction when combined with standard drugs. CuONPs exhibited significant cytotoxicity against non-small cell lung cancer with an IC50 value of 100.8 µg ml-1 for A549 and 88.3 µg ml-1 for the H1299 cell line with apoptotic activities. Furthermore, biogenic CuONPs was evaluated for their photocatalytic degradation potential against methylene blue dye and were able to removed 94% dye in 90 min. Free radical scavenging analysis suggested that CuONPs assisted dye degradation was mainly induced by hydroxide radicals. Biogenic CuONPs appears as an eco-friendly and cost effective photocatalyst for the treatment of wastewater contaminated with synthetic dyes that poses threat to aquatic biota and human health. The present study highlighted the blend of biomedical and photocatalytic potential of Phormidium derived CuONPs as an attractive approach for future applications in nanomedicine and bioremediation.

Dataset Information

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

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Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

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