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Title: Molecular mechanisms of cadmium toxic
Author: Lawal, Akeem Olalekan
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2009
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Cadmium is a heavy metal which has been associated with a number of pathological diseases. However, despite the known toxicity of this metal, there is inconclusive evidence about its mechanism(s) of action in the cells. The present study was therefore undertaken with the aim of defining the role of oxidative stress, intracellular Ca²⁺ alteration via phospholipase C- Inositol-1,4,5-triphosphate (PLC-IP3) and mitochondrial-cytochrome c dependent pathways in the etiology of cadmium-induced toxicity in three human cell lines: HepG2 (human hepatoma), 1321N1 (human astrocytoma) and HEK 293 (human embryonic kidney) cell lines after 24hrs exposure to 5, 10 and 50 μM cadmium chloride (CdCl₂). The role of the Nrf2-Keap1-ARE pathway in the adaptive response of these cell lines to Cd exposure was examined, and the possible mechanism(s) involved in the protective response of garlic extracts to CdCl₂ were also investigated. Finally, this work examined changes in the proteomic profile of the three human cell lines after Cd exposure in order to develop suitable biomarkers for Cd toxicity. In summary, this study shows that the oxidative stress induced by Cd occurs by different mechanisms depending on cell type and that Ca²⁺ alteration may play an important role in Cd-induced toxicity in HEK 293 cells, while the mitochondrial-cytochrome c dependent pathway is important in Cd toxicity in all three cell lines. Also, the study shows that Nrf2-Keap1-ARE mediated adaptive response to Cd may be activated by PKCδ and that Cd generally alters the metabolism of exposed cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available