Cytotoxic effects of silver nanoparticles to embryonic zebrafish (Danio Rerio) Cells: Focussing on the development of alternative models for Nano (Eco)Toxicity studies

Carrazco Quevedo, Ana Isabel ORCID: 0000-0002-0233-3576 (2022). Cytotoxic effects of silver nanoparticles to embryonic zebrafish (Danio Rerio) Cells: Focussing on the development of alternative models for Nano (Eco)Toxicity studies. University of Birmingham. Ph.D.

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Abstract

This thesis presents an initial evaluation of the utility of adherent embryonic zebrafish fibroblast cells (ZF4) as a potential early-stage aquatic in vitro model for nanosafety evaluation, assessing the molecular and toxicological responses activated by exposure to silver nanoparticles (AgNPs) of different sizes and their ionic counterpart (AgNO3). A range of characterisation methods were implemented to evaluate changes in the physico- chemical properties of AgNPs, such as hydrodynamic size, zeta potential, polydispersity index, dissolution and agglomeration in the different exposure media used, including cell culture media supplemented with 10 % serum (CCM), serum-free media (SFM) and ultra- pure water (UPW). The biological responses of the ZF4 cells were assessed by exposing the cells to three representative AgNP sizes (10, 30 and 100 nm) and three concentrations of the NPs (2.5, 5 and 10 μg/mL) and AgNO3 (1, 1.5 and 2 μg/mL) determined on the basis of a 24-hour cytotoxicity exposure, representing low, medium, and high (EC50) concentrations, respectively.

To conclude, fibroblast-like ZF4 cells have great potential to be used as an aquatic early- stage in vitro model for nanotoxicity studies, providing insights about the toxicity of AgNPs. The responses to the AgNPs in ZF4 cells were comparable to responses reported for similar NPs in other fish cell and mammalian models. In addition, our results provide insights about the molecular events triggered as part of a cytotoxic response, potentially contributing to the establishment of Adverse Outcome Pathways (AOP), and in support of efforts towards reduction of animal experimentation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):