title: Differential effects and potential adverse outcomes of ionic silver and silver nanoparticles in vivo and in vitro.
abstract: Nanoparticles are of concern because of widespread use, but it is unclear if metal nanoparticles cause effects directly or indirectly. We explored whether polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) cause effects through intact nanoparticles or dissolved silver. Females of the model species fathead minnow (Pimephales promelas) were exposed to either 4.8 μg/L of AgNO3 or 61.4 μg/L of PVP-AgNPs for 96h. Microarray analyses were used to identify impacted receptors and toxicity pathways in liver and brain tissues that were confirmed using in vitro mammalian assays. AgNO3 and PVP-AgNP exposed fish had common and distinct effects consistent with both intact nanoparticles and dissolved silver causing effects. PVP-AgNPs and AgNO3 both affected pathways involved in Na(+), K(+), and H(+) homeostasis and oxidative stress but different neurotoxicity pathways. In vivo effects were supported by PVP-AgNP activation of five in vitro nuclear receptor assays and inhibition of ligand binding to the dopamine receptor. AgNO3 inhibited ligand binding to adrenergic receptors α1 and α2 and cannabinoid receptor CB1, but had no effect in nuclear receptor assays. PVP-AgNPs have the potential to cause effects both through intact nanoparticles and metal ions, each interacting with different initiating events. Since the in vitro and in vivo assays examined here are commonly used in human and ecological hazard screening, this work suggests that environmental health assessments should consider effects of intact nanoparticles in addition to dissolved metals.
authors.affiliation: Institute for Genomics Biocomputing and Biotechnology, Mississippi State University , Starkville, Mississippi 39759, United States.
authors.forename: Natàlia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kennedy
authors.forename: B Lynn
authors.initials: BL
authors.lastname: Escalon
authors.forename: Tanwir
authors.initials: T
authors.lastname: Habib
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Laird
authors.forename: Arun
authors.initials: A
authors.lastname: Rawat
authors.forename: Steven
authors.initials: S
authors.lastname: Wiseman
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.forename: Nancy
authors.initials: N
authors.lastname: Denslow
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Steevens
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Perkins
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016000:Cluster Analysis; D003530:Cyprinidae / Q000378:metabolism*; D057075:Enzyme Assays; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011205:Povidone / Q000633:toxicity; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D012835:Silver Nitrate / Q000633:toxicity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D012834:Silver; D012835:Silver Nitrate; D011205:Povidone