Nanoparticle toxicity and molecular mechanisms in fish: A case study with silver nanoparticles

<p>Nanoparticles (NPs) are widely used in a myriad of commercial and industrial products making their entry to the environment a likely event. NPs have unique physical-chemical properties that result from their small size and high surface area to volume ratio, making them highly reactive and potentially toxic. In Chapter 1, we summarize the effects and mechanisms of metal-based NPs on the vascular system. <em>In vitro</em> studies have shown that NPs are anti-angiogenic because they cause inflammation, oxidative stress, and apoptosis of endothelial cells resulting in increased permeability and decreased proliferation and migration. Whole animal studies examining the effects of NPs on the vascular system are scarce and although the few available studies do not disproof the anti-angiogenic properties of NPs, the mechanisms and long-term effects of these changes are poorly understood. Considering the key physiological role of the vascular system, there is a need for more studies in this area. In Chapter 2, we show that blood proteins can quickly bind to the surface of NPs, which might greatly change their biological identity. We present novel data on the formation of a “protein corona” (PC) after incubation of polyvinylpyrrolidone-coated AgNPs (PVP-AgNPs, 50 nm) in fish (smallmouth bass) plasma. Both gender and length of incubation affected the types of proteins identified from PC. The most common proteins were related to immune function, red blood cell function and clotting, and lipid and cholesterol transport. Vitellogenin and zona pellucida egg proteins were only detected in PCs incubated with female plasma. We propose that fish plasma serves as a good media for the characterization of PC in future studies with NPs and that binding of egg proteins to the surface of PVP-AgNPs could result in enhanced movement of particles to developing oocytes and maternal transfer to developing embryos. In Chapter 3, vascular effects of PVP-AgNPs ( 60 nm) were evaluated on transgenic zebrafish (TG fli1a: EGFP) embryos. Exposure to 1 and 10 mg/L PVP-AgNPs during the period of vascular development caused a delay in vascular development; however, expression of genes within the vascular endothelia growth factor (VEGF) signaling pathway was enhanced. This apparent contradiction was explained by the induction of hypoxic conditions in the embryo via agglomeration of NPs on the surface of eggs. Hypoxia is a potent stimulant of the VEGF signaling pathway, but blood vessel development is not enhanced because no increased production in VEGF protein was observed, likely because of impaired translation due to AgNP toxicity to the endoplasmic reticulum. In Chapter 4, we evaluated the toxicity of a commercial product (socks) containing AgNPs. Importantly, we demonstrate that the toxicity of this leachate to zebrafish embryos was not due to AgNPs, but instead to the presence of unknown chemical(s). At the time this study was published, there was no data on the toxicity of AgNPs released from any commercial products. Overall, this set of studies advances our current understanding on the mechanisms of toxicity of AgNPs by providing novel molecular and whole animal data that can be used for future risk assessment for this emerging class of contaminants.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Forestry and Natural Resources

Year

2016

Author dc:creator

• Gao, Jiejun

Contributors dc:contributor

• Maria S. Sepulveda
• Henry C. Chang
• Qing Deng
• Cecon T. Mahapatra
• Alexander Wei

• Health and environmental sciences
• Fish
• Molecular mechanisms
• Nanoparticles
• Toxicity
• Surgery
• Toxicology

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/925

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-2146