Orientador: Prof. Dr. Ricardo Pereira Ribeiro

 Data da Defesa: 25/03/2019

Curcumin is a phytochemical compound proven from turmeric (Curcuma longa) which is given by its strong pigment, being vigorously applied as a spice in Indian and South Asian cuisine. It has broad properties, antioxidants and anti-inflammatory. Similarly, it is applied in research as a nutraceutical for the prevention and treatment of diseases such as Alzheimer's, diabetes, cancer, cardiovascular diseases and immunodepressed.
Zebrafish (Danio rerio), popularly known as paulistinha, has been used as an experimental model for the study of diseases in general. Because it has external fertilization, this provides embryonic studies that are complete in 3 days post fertilization, present lower costs when compared to the murine models, reproductions in larger numbers in a shorter time interval. Toxicity assays in Zebrafish models are prevalently applied by industries, with a higher incidence in the pharmaceutical industry, in order to determine the safety of compounds and obtain regulatory approval for clinical trials.
The objective of the present study was to evaluate the toxicity that it can present when used at different levels of concentrations, based on results expressed in possible malformations and survival rate.
A curcumin solution was prepared in DMSO medium to acquire a subsequently used aliquot solution for serial dilution in dechlorinated water from the medium. Adult fish (<18 months of age) were used under appropriate conditions of luminosity, temperature and pH for the acquisition of embryos 0 hours post fertilization for the toxicity test at different concentration levels of curcumin obtained from the serial dilution .
Statistical analysis was performed using GraphPad Prism software (GraphPad 6 Software, La Jolla, California, USA) for analysis of variance by ANOVA using the Dunnett test. The log-rank test was used to calculate the statistical differences in the survival of the different experimental groups.
Curcumin is a bioactive substance, responsible for performing diverses nutraceutical properties, acting to treat some diseases and vital maintenance of organism. Being it is a phenolic compound derived from tumeric, is known as a strong natural anti-oxidant, exerting a reduction in the oxidative stress of cells and in the formation of free radicals, contributing to anti-inflammatory and anticarcinogenic actions. However, when zebrafish embryos were exposed to high concentrations of curcumin for a continuous period of 96 hours, there was an opposite-than-expected effect. At concentrations of 5 and 6.25 μM / mL curcumin, the presence of few teratogenic characteristics in the embryonic development, with a high survival rate, was observed and recommended to be a safe concentration; at concentrations of 10 and 12.5 μM / mL, 35% appeared for some deformities and a low survival rate of less than 50%, indicating that the concentrations were untreated because of the risk of toxicity; for the 25, 50 and 100 μM / mL concentrations the survival rate was 0% from the first 25 hours of exposure, indicating to be highly toxic doses. This phenomenon was due to high concentrations, time of exposure, indicating that the drug has adverse effects, increasing the oxidative stress of the cells and the formation of free radicals
For a long time curcumin has been used as a nutraceutical compound for maintenance of human health, since its great influence in Asian culture and later spread throughout the continents. In summary, our results confirm that high concentrations of curcumin may cause a wide range of adverse consequences in embryonic development of zebrafish, including levels of partial or total lethality, as well as severe or mild teratogenic characteristics, according to the concentration applied in a period of 96 hours, satisfying the need to previously identify safe compound concentrations for any therapeutic purpose.
Keywords: curcumin, embryotoxicity, zebrafish.


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