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Exposi??o de embri?es e larvas de zebrafish a compostos bisfen?licos para elucida??o de mecanismos neurotoxicol?gicosFonseca, Raphaela Soares 26 February 2018 (has links)
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Previous issue date: 2018-02-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The increase of environmental pollutants sources directly affects the ecosystem and human health, mainly due to loss of soil and water quality. Among these toxic agents are included endocrine disruptors, which can cause changes in biochemical pathways and physiological changes in organisms. Studies with different forms of bisphenols, compounds present in many products of human consumption and the environment, had already demonstrated extremely adverse effects on behavior and gene expression of targets related to neural and endocrine systems during development. The zebrafish, Danio rerio, is an excellent model organism for studying neurotoxicity, due to its advantages with respect to specific aspects of their development and a low maintenance cost when compared to other vertebrate model organisms. This work proposes the investigation of the effects of bisphenol A (BPA), its chlorinated derivatives and its substitutes (BPS and BPF), toxicological and behavioral parameters combined with characterization of its potential underlying cellular and molecular mechanisms such as cell death and proteins and gene expression in the nervous and endocrine systems. After the embryo and larvae were exposed to different concentrations of BPA and its derivatives, morphological analyzes and embryo survival were carried out, as well as behavioral tests of locomotion and cognitive evaluation of the larvae. In the concentrantion curve of the different bisphenolic compounds, no significant difference was observed in the survival, teratogenesis and hatching of the animals, however, a significant increase was detected in the exploratory parameters of the BPA and BPF groups. When comparing the aversive behavior of the BPA with the DMSO, there was no statistical difference between the groups, whereas in the BPS an improvement in the escape response of the larvae occurred. Additionally, behavioral and locomotor activity analyzes will be performed in adult animals previously treated with the compounds studied during the initial development. In this way, it is expected to contribute to the current knowledge of neurotoxicity mechanisms related to endocrine disruption caused by contaminants of the bisphenol family. / O crescimento das fontes de poluentes ambientais afeta diretamente o ecossistema e a sa?de humana, principalmente devido ? perda da qualidade do solo e da ?gua. Entre estes agentes t?xicos, est?o inclu?dos os disruptores end?crinos, os quais podem acarretar diversas mudan?as em vias bioqu?micas e altera??es fisiol?gicas em organismos. Estudos com diferentes formas de bisfen?is, compostos presentes em diversos produtos de consumo humano e inclusive no ambiente devido ? contamina??o por efluentes industriais, j? apresentaram efeitos extremamente nocivos na regula??o da express?o de genes relacionados ao sistema neural e end?crino durante o desenvolvimento, al?m de altera??es comportamentais severas. O zebrafish, Danio rerio, ? um excelente organismo modelo para estudar neurotoxicidade, uma vez que possui vantagens em rela??o a aspectos espec?ficos do seu desenvolvimento e um custo reduzido de manuten??o quando comparado a outros vertebrados modelos. Este projeto prop?s o estudo dos efeitos do bisfenol A (BPA), seus derivados clorados e substitutivos (BPS e BPF), sobre par?metros de embriotoxicidade e comportamento, buscando tamb?m caracterizar os mecanismos celulares e moleculares dos potenciais efeitos observados avaliando morte celular e n?veis de prote?nas e express?o de genes alvos em embri?es e larvas de zebrafish. Para tanto, ap?s a exposi??o dos embri?es e larvas a diferentes concentra??es de BPA e seus derivados, foram realizadas an?lises morfol?gicas e sobreviv?ncia dos embri?es; ensaios comportamentais de locomo??o e avalia??o cognitiva das larvas. Ao realizar a curva de concentra??o dos diferentes compostos bisfen?licos, n?o foi observada diferen?a significativa na sobreviv?ncia, teratog?nese e eclos?o dos animais, por?m, ao analisar o comportamento explorat?rio dos animais tratados com BPA e BPF foi detectado um aumento significativo nos par?metros explorat?rios das larvas. Ao compararmos o comportamento aversivo do BPA com o controle tratado com o ve?culo DMSO, n?o existiu diferen?a estat?stica entre os grupos, enquanto no BPS ocorreu uma melhora na resposta de escape das larvas. Adicionalmente, ser?o realizadas an?lises comportamentais e de atividade locomotora em animais adultos previamente tratados com os compostos estudados durante o desenvolvimento inicial. Desta forma, espera-se contribuir para o conhecimento atual dos mecanismos de neurotoxicidade relacionados ? disrup??o end?crina causada por contaminantes da fam?lia dos bisfen?is.
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