|Title:||The endothelial response to arecoline|
|Publisher:||University of Sydney.|
Faculty of Dentistry.
|Abstract:||Oral submucous fibrosis (OSF) is a premalignant fibrotic condition of the oral cavity associated with areca nut use, and involves reduced mucosal vascularity. The areca nut alkaloid arecoline has known toxicity for epithelium and fibroblasts, and this thesis describes similar toxicity for endothelium. Cultured Human Umbilical Vein Endothelial Cells were exposed to increasing concentrations of arecoline. Cytotoxicity was assessed by phase contrast microscopy, haemocytometer counts, transmission electron microscopy, and LDH and MTT assays. Culture supernatants and lysates from equivalent parallel cultures were tested by ELISA for a range of relevant cytokines being bFGF, IL-1alpha, IL1beta, IL-6, GM-CSF, and G-CSF. Characterization of mRNA expression extracted after 4 and 10 hour was performed by RT PCR and micro-array. Arecoline was frankly cytotoxic at and above 333 g/ml while ultrastructural features of cellular stress were observed at lower concentrations. bFGF was up regulated at protein level while other proinflammatory cytokines were down regulated at both protein and mRNA level with increasing concentrations of arecoline. Significant alterations in gene expression profile related to cellular stresses, inflammation and immune responses were seen. Arecoline is cytotoxic for human endothelium while important cellular stress responses at lower concentrations may contribute to the initiation and progression of OSF.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
|ULLAH Mafaz - Final Thesis.pdf||Final thesis||48.3 MB||Adobe PDF|
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