title: Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).
abstract: Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to humans and other organisms leading to potential adverse health effects. The aim of the present study is to evaluate the effects of early life exposure to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio). Previously published data has suggested that PVP-AgNP exposure can inhibit the expression of genes within the vascular endothelial growth factor (VEGF) signaling pathway, leading to delayed and abnormal vascular development. Here, we show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP-AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in VEGF-related gene expression that returns to baseline levels at hatching (72 hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular development. Interestingly, increased gene transcription was not followed by the production of associated proteins within the VEGF pathway, which we attribute to NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may be responsible for the observed delays in vascular development at later stages, and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were < 0.001 mg/L at all times, with no significant effects on the VEGF pathway. We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress.
authors: a Department of Forestry and Natural Resources and Bindley Biosciences Center .
authors: Jiejun
authors: J
authors: Gao
authors: a Department of Forestry and Natural Resources and Bindley Biosciences Center .
authors: Cecon T
authors: CT
authors: Mahapatra
authors: b Department of Animal Sciences , and.
authors: Christopher D
authors: CD
authors: Mapes
authors: c Department of Chemistry , Purdue University , West Lafayette, IN , USA.
authors: Maria
authors: M
authors: Khlebnikova
authors: c Department of Chemistry , Purdue University , West Lafayette, IN , USA.
authors: Alexander
authors: A
authors: Wei
authors: a Department of Forestry and Natural Resources and Bindley Biosciences Center .
authors: Marisol S
authors: MS
authors: Sepúlveda
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002319:Cardiovascular System / Q000187:drug effects* / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012834:Silver
keywords: Nanoparticles; VEGF pathway; vascular toxicity; zebrafish embryos