The FDA-approved platinum compound, cisplatin, is commonly used as a chemotherapy drug to treat many forms of cancer. However, this compound also has several associated side-effects, including ototoxicity. This has made the development of novel platinum compounds that reduce cancer cell viability, while causing fewer and milder side-effects, an area of significant research interest. In the present study, we examined the apoptotic effects that four monofunctional platinum compounds, pyriplatin, phenanthriplatin, Pt(diethylenetriamine)Cl, and Pt(N,Ndiethyldiethylenetriamine) Cl, had on zebrafish inner ear auditory epithelial cells. We then compared the apoptotic effects of these compounds to those of cisplatin, which is a bifunctional platinum compound. Our hypothesis was that the four monofunctional platinum compounds would cause reduced inner ear apoptosis compared to cisplatin. Zebrafish were injected with either vehicle solution, cisplatin or with one of the monofunctional compounds. Later, at 24-hour and 48-hour time points, the zebrafish were euthanized, and two of their auditory inner ear endorgans, the utricle and saccule, were dissected out. A terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay was then used to label apoptotic cells, and the inner ear organs were viewed under a microscope. The number of apoptotic cells on each sample was quantified and the data were analyzed for significant differences between treatments. We found that with the exception of pyriplatin in the saccules, and with the exception of pyriplatin, Pt(N,N-diethyldiethylenetriamine)Cl, and phenanthriplatin in the utricles, the monofunctional compounds and cisplatin did not induce apoptosis in the inner ear of zebrafish at either time point. Based on these results we conclude that the monofunctional platinum compounds largely do not induce zebrafish inner ear apoptosis and if they were to produce ototoxicity, it would not be through an apoptotic mechanism.
| Identifer | oai:union.ndltd.org:WKU/oai:digitalcommons.wku.edu:theses-3345 |
| Date | 01 April 2018 |
| Creators | Smith, Joshua |
| Publisher | TopSCHOLAR® |
| Source Sets | Western Kentucky University Theses |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses & Specialist Projects |
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