Etude de la biodistribution et de la toxicité des Nanoparticules de Fer chez le rat et sur une lignée de neuroblastome

Abstract : Iron Oxide Nanoparticles (IONPs) are used in several fields notably in Biomedicine as theranostic agents in Oncology and also as contrast agents in Magnetic Resonance Imaging. With the increase in the production and use of IONPs, there is a clear increase in human and environmental exposure to these NPs, which may pose a risk. The subject of my thesis is the study of the physiopathological impact and toxicity of iron oxide nanoparticles using a cell model of neuroblastoma and an animal study model, the Wistar rat. The aim of the research work of the in vitro part is to evaluate the cytotoxic and genotoxic effects as well as the effects on the expression of cellular proteins following the exposure of SH-SY5Y cells to increasing concentrations of iron NPs. We have shown that iron NPs induce cellular perturbations in a size and concentration dependent manner. Proteomic analysis followed by ontological gene annotation and signaling pathway analysis revealed the effects of IONPs on cytoskeleton, apoptosis and cancer development. The aims of our research carried out in vivo are to investigate the pathophysiological effects of iron NPs administered by three different routes, intravenous, intranasal and oral, also their impact on emotional and cognitive behavior as well as neurotransmitter and trace element homeostasis. The results showed that IONPs do not induce any changes in anxiety, locomotion, learning and memory in rats regardless of the administration route. However, these NPs cause a disruption of catecholamine and trace element levels in the brain. The most marked effects have been observed following intranasal instillation of NPs and are manifested by a decrease in serum iron levels, thrombocytosis and the presence of inflammatory foci in the liver. The comparative analysis of the three routes of administration showed that the intravenous route is the least toxic. Finally, the proteomic study of the proteomes of the brain, liver and lung has made it possible to evaluate the toxicity of the NPs of iron at the protein and molecular level. The obtained results provide an important support for the estimation and understanding of potentially adverse effects of these NPs, which have a certain toxicity that is not negligible from a molecular and physiopathological point of view. Thus, great care must be taken regarding their use in the biomedical field to minimize any risk related to IONP exposure in order to improve their biocompatibility and thus increase their benefits.
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Dalel Askri. Etude de la biodistribution et de la toxicité des Nanoparticules de Fer chez le rat et sur une lignée de neuroblastome. Médecine humaine et pathologie. Université Grenoble Alpes; Université de Carthage (Tunisie), 2018. Français. ⟨NNT : 2018GREAS021⟩. ⟨tel-02384612⟩

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