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Étude toxicologique de nanoparticules polymériques véhicules de S-nitrosoglutathion

Abstract : Although nanoparticles (NP) are more and more used in medicine (diagnosis, imaging, drug targeting), few studies on their possible undesirable effects have been conducted. The aim of this work was to evaluate the effects of polymeric NP Eudragit® RL loaded or not with S-nitrosoglutathione (GSNO), a nitric oxide donor, using two different cell lines: monocytes/macrophages of rat (NR8383) and human (THP-1). First, our results show that exposure to blank NP Eudragit® induced an up-regulation of ATG16L, BCL2 and TNFA and a down-regulation of PDCD4 in rat cells, what are in favor of a repression of apoptosis and an induction of autophagy. On the other hand, NCF1, NFKB, and IL1B were down-regulated in human cells, which may contribute to explain the increase of cellular viability. Second, we evaluated the effects of these NP loaded or not with GSNO on THP-1 cells. The results show that NP Eudragit® were internalized by cells using likely the clathrine and caveoline endocytic pathways. Transcriptome analyses by microarray of THP-1, exposed to either GSNO-loaded or empty NP, have shown a significant dose and time-dependent variation of the expression of genes belonging to the clusters “proliferation”, “cell structure” for the empty NP and “mitochondria” and “metabolic processes” for the loaded ones. These results are consistent with those of cellular assays. Transcriptome analyses of free GSNO allowed to propose a mechanism of non-specific immunity activation against Leishmania in the macrophage. Thus, (i) the cytotoxicity of NP is cellular model dependent and (ii) mechanistic toxicology should be the corner stone for the evaluation of NP harmfulness
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  • HAL Id : tel-01595791, version 1

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Ramia Safar. Étude toxicologique de nanoparticules polymériques véhicules de S-nitrosoglutathion. Médecine humaine et pathologie. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0213⟩. ⟨tel-01595791⟩

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