EFEITO DOS EXTRATOS DE TUCUMÃ (Astrocaryum aculeatum) LIVRES E NANOEMULSIONADO NA INDUÇÃO DA DIFERENCIAÇÃO CELULAR POR VIA GÊNICA E PARTICIPAÇÃO DO METABOLISMO OXIDATIVO EM CÉLULAS NB4-LPA

• Autor(a) principal: COPETTI, Priscila Marquezan
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional Universidade Franciscana
• Texto Completo: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/733
• topic: Citotoxicidade. Nanotecnologia. PML/RARa. Síndrome de diferenciação. Tucumã.; Cytotoxicity. Nanotechnology. PML/RARα. Differentiation syndrome. Tucumã.; Nanociências

Acute promyelocytic leukemia is characterized by the translocation between chromosomes 15 and 17 (PML and RARα genes) which is responsible for cellular immaturity with exacerbated proliferation of promyelocytes developing the symptoms of this disease, mainly severe hemorrhagic crises. The involvement of the RARα gene enables the target molecular treatment with the synthetic chemotherapy ATRA however patients have demonstrated resistance to treatment especially in relapsed cases, still may develop a syndrome differentiation due to toxic doses at the start of treatment and maintaining this. Alternatively, to the synthetic ATRA and considering the promising researches with bioactive substances and natural compounds was invested in a fruit from the Brazilian Amazon known for its biodiversity and potential for discovering new plants for therapeutic purposes. The tucumã is rich in several substances among these, carotenoids. Still, nanotechnology can also be an alternative the difficulties of this disease. Nanoemulsions were produced so that they could aid in protection of active increase solubility and improve the biodistribution of lipophilic substances. The objective of this study was to evaluate the in vitro effect of hydroalcoholic extracts of tucumã in free and nanoemulsified forms, and of the drug ATRA in acute promyelocytic leukemia cells (NB4-LPA) and the participation of oxidative metabolism. The results indicated that the concentration of 100 μg/mL of the pulp reversed the chromosomal translocation, maintaining cell viability and induced the caspase level. The synergism between extract and ATRA was able to control the ATRA toxicity and potentiate its effects, inducing apoptosis and reversing chromosome translocation. In view of these results, the nanoemulsion formulations produced were suitably developed and exhibited appropriate refrigeration stability up to 90 days of analysis. The formulations of nanoemulsions with extract were more effective than the free extract in the tested concentrations. It is concluded that the investment in natural substances and the growing study of nanotechnology can be an effective alternative to circumvent the obstacles that some treatments have been presenting, but it is essential that the methods of analysis are as varied and appropriate as possible for each target.