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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

SUBMITTER: Gao J

PROVIDER: S-EPMC5319437 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

Gao Jiejun J Mahapatra Cecon T CT Mapes Christopher D CD Khlebnikova Maria M Wei Alexander A Sepúlveda Marisol S MS

Nanotoxicology 20160808 9

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 wi ...[more]

PMID: 27499207

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Project description:Glutathione (GSH), the most abundant vertebrate endogenous redox buffer, plays key roles in organogenesis and embryonic development, however, organ-specific GSH utilization during development remains understudied. Monochlorobimane (MCB), a dye conjugated with GSH by glutathione-s-transferase (GST) to form a fluorescent adduct, was used to visualize organ-specific GSH utilization in live developing zebrafish (Danio rerio) embryos. Embryos were incubated in 20 μM MCB for 1 h and imaged on an epifluorescence microscope. GSH conjugation with MCB was high during early organogenesis, decreasing as embryos aged. The heart had fluorescence 21-fold above autofluorescence at 24 hpf, dropping to 8.5-fold by 48 hpf; this increased again by 72 hpf to 23.5-fold, and stayed high till 96 hpf (18-fold). The brain had lower fluorescence (10-fold) at 24 and 48 hpf, steadily increasing to 30-fold by 96 hpf. The sensitivity and specificity of MCB staining was then tested with known GSH modulators. A 10-min treatment at 48 hpf with 750 μM tert-butylhydroperoxide, caused organ-specific reductions in staining, with the heart losing 30% fluorescence, and, the brain ventricle losing 47% fluorescence. A 24 h treatment from 24-48 hpf with 100 μM of N-Acetylcysteine (NAC) resulted in significantly increased fluorescence, with the brain ventricle and heart showing 312% and 240% increases respectively, these were abolished upon co-treatment with 5 μM BSO, an inhibitor of the enzyme that utilizes NAC to synthesize GSH. A 60 min 100 μM treatment with ethacrynic acid, a specific GST inhibitor, caused 30% reduction in fluorescence across all measured structures. MCB staining was then applied to test for GSH disruptions caused by the toxicants perfluorooctanesulfonic acid and mono-(2-ethyl-hexyl)phthalate; MCB fluorescence responded in a dose, structure and age-dependent manner. MCB staining is a robust, sensitive method to detect spatiotemporal changes in GSH utilization, and, can be applied to identify sensitive target tissues of toxicants.

Dataset Information

Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

Publications

Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

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