title: Enhanced toxicity of silver nanoparticles in transgenic Caenorhabditis elegans expressing amyloidogenic proteins.
abstract: The increasing number of applications of silver nanoparticles (AgNP) prompted us to assess their toxicity in vivo. We have investigated their effects on wild type and transgenic Caenorhabditis elegans (C. elegans) strains expressing two prototypic amyloidogenic proteins: β2-microglobulin and Aβ peptide3-42. The use of C. elegans allowed us to highlight AgNP toxicity in the early phase of the worm's life cycle (LC50 survival, 0.9 µg/ml). A comparative analysis of LC50 values revealed that our nematode strains were more sensitive to assess AgNP toxicity than the cell lines, classically used in toxicity tests. Movement and superoxide production in the adult population were significantly affected by exposure to AgNP; the transgenic strains were more affected than the wild type worms. Our screening approach could be applied to other types of nanomaterials that can enter the body and express any nanostructure-related bioactivities. We propose that C. elegans reproducing the molecular events associated with protein misfolding diseases, e.g. Alzheimer's disease and systemic amyloidosis, may help to investigate the specific toxicity of a range of potentially harmful molecules. Our study suggests that transgenic C. elegans may be used to predict the effect of chemicals in a "fragile population", where an underlying pathologic state may amplify their toxicity.
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .
authors.forename: Cristina
authors.initials: C
authors.lastname: Soria
authors.affiliation: b Laboratory of Experimental and Clinical Toxicology, Toxicology Division, Department of Environmental Medicine , IRCCS Salvatore Maugeri Foundation, Scientific Institute of Pavia Medical Centre , Pavia , Italy .
authors.forename: Teresa
authors.initials: T
authors.lastname: Coccini
authors.affiliation: c Toxicology Unit, Department of Clinical Surgical , Diagnostic and Pediatric Sciences, Faculty of Medicine and Surgery, University of Pavia , Pavia , Italy .
authors.forename: Uliana
authors.initials: U
authors.lastname: De Simone
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .
authors.forename: Loredana
authors.initials: L
authors.lastname: Marchese
authors.affiliation: d Department of Internal Medicine and Clinical Therapeutics , University of Pavia , Pavia , Italy .
authors.forename: Irene
authors.initials: I
authors.lastname: Zorzoli
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .|e Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London , London , UK , and.
authors.forename: P Patrizia
authors.initials: PP
authors.lastname: Mangione
authors.affiliation: f Bioengineering Laboratory, Department of Computer , Electrical and Biomedical Engineering, University of Pavia , Pavia , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ramat
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .|e Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London , London , UK , and.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
authors.affiliation: b Laboratory of Experimental and Clinical Toxicology, Toxicology Division, Department of Environmental Medicine , IRCCS Salvatore Maugeri Foundation, Scientific Institute of Pavia Medical Centre , Pavia , Italy .|c Toxicology Unit, Department of Clinical Surgical , Diagnostic and Pediatric Sciences, Faculty of Medicine and Surgery, University of Pavia , Pavia , Italy .
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzo
authors.affiliation: a Department of Molecular Medicine , Institute of Biochemistry, University of Pavia , Pavia , Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
mesh_terms: D058227:Amyloidogenic Proteins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry*
chemical_list: D058227:Amyloidogenic Proteins; D017382:Reactive Oxygen Species; D012834:Silver
keywords: Amyloidosis; C. elegans; nanoparticles; nanotoxicology