Modulação da neurotransmissão colinérgica como resposta aos efeitos causados pela exposição a nanopartículas de óxido de ferro revestidas com dextran-aminado utilizando zebrafish (Danio rerio) como modelo de estudo

• Autor(a) principal: Oliveira, Giovanna Medeiros Tavares de
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
• Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/5475
• topic: BIOLOGIA MOLECULAR; BIOQUÍMICA; NEUROBIOLOGIA; NEUROTRANSMISSORES; TOXICOLOGIA; PEIXES - PESQUISAS; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent in magnetic resonance imaging and as a targeted drug delivery system with good biocompatibility. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity. For this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked and aminated dextran (CLIO-NH2) were synthesized by the co-precipitation method and characterized by transmission electron microscopy (TEM) and light scattering dynamics. The analysis of the elementary composition of the solution at the end of the synthesis was also performed. The magnetite core size was 5.5 ± 1.4 nm, on a concentration of 10 mg Fe-NPs/ml. We have evaluated the effects of different CLIO-NH2 doses (20, 50, 100, 140 and 200 mg/kg) as a function of time after exposure (one, 16, 24 and 48 hours) on AChE activity and ache expression in zebrafish brain. At tested concentrations, only the animals exposed to 200 mg/kg, and assessed 24 h after administration of the nanoparticles, have shown decreased AChE activity. These values returned to control levels after 48 h of exposition, indicating a transitory toxical effect. The RT-qPCR results suggested that inhibition of brain AChE is not directly related with the transcriptional control, and it was probably due to post-transcriptional events. Once ACh is recognized to play an important role in the regulation of locomotor control, we further evaluated parameters of zebrafish swimming activity. CLIO-NH2 at 200mg/kg, evaluated after 24 h, also impaired all the tested parameters of zebrafish swimming activity, i.e. decreased traveled distance, mean speed, number of line crossings, and turn angle. We further investigated the iron accumulation in zebrafish brain by ICP-MS, and a significant higher level of ferric iron was found in zebrafish brains exposed to CLIO-NH2. In summary, the results presented herein provide further experimental evidence that exposure to high doses of dextran-coated iron oxide nanoparticles can be transiently neurotoxic.