Integrated In vitro - Omics based Approach to assess the Heavy metals and their Binary mixtures toxicity in Hippocampal HT-22 cell line

Identificador:  TDX:2788

Handle: https://hdl.handle.net/20.500.11797/TDX2788

Autores:  Karri, Venkatanaidu

Resumen:
Environmental exposures are virtually always to complex metal mixtures. Current toxicological studies dictate a largely metal-by-metal evaluation of exposures and risks in brain, which fails to adequately address potential interactions of metals in hippocampus region of brain. We evaluated the similar/dissimilar neurotoxicity of each metal in brain that can give strong support to the mixtures effect in brain (Chapter 1). The scope of our study is to proving the single metal (Pb, Cd, As, and MeHg) and their mixtures chronic toxicity impact in HT-22 hippocampal cell line by using the in vitro and system biology methodology. Initially, we performed the cytotoxicity, apoptosis, and genotoxicity assays of single metals for assessing the toxicity potency of each metal, their mixtures interactions profile in hippocampal cells (Chapter 2, 3). The obtained results clearly showed the potency of metals MeHg> As>Cd>Pb. Another aim of the study (Chapter 4) was the heavy metals toxicity in HT- 22 cells using (Pb, Cd, As, and MeHg), as some stress proteins could be considered as biomarkers for heavy metals. Identification of these proteins and their mapping into specific cellular processes may help to gain deeper insight into the toxic mechanisms of heavy metals in hippocampus. Analysis of the stress response of HT-22 cells to metal mixtures was another aim of the study (Chapter 5) to identify proteins, which are involved in the neurodegeneration mechanism.