Investiga??o da toxicidade gen?tica de produtos naturais atrav?s de bioensaios de curta dura??o

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Bibliographic Details
Main Author: Cruz, Marina Sampaio de Menezes
Other Authors: 91206359072
Language:Portuguese
Published: Universidade Federal do Rio Grande do Norte 2016
Subjects:
Online Access:http://repositorio.ufrn.br/handle/123456789/20332
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Summary:Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-26T19:16:13Z No. of bitstreams: 1 MarinaSampaioDeMenezesCruz_DISSERT.pdf: 1274699 bytes, checksum: f39afb06729aedccb850680b592f9def (MD5) === Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-28T22:46:18Z (GMT) No. of bitstreams: 1 MarinaSampaioDeMenezesCruz_DISSERT.pdf: 1274699 bytes, checksum: f39afb06729aedccb850680b592f9def (MD5) === Made available in DSpace on 2016-04-28T22:46:18Z (GMT). No. of bitstreams: 1 MarinaSampaioDeMenezesCruz_DISSERT.pdf: 1274699 bytes, checksum: f39afb06729aedccb850680b592f9def (MD5) Previous issue date: 2015-07-30 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) === Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) === Os produtos naturais derivados de plantas servem de mat?ria-prima para a s?ntese de fitoter?picos, sendo amplamente utilizados por v?rias popula??es em todo o mundo. Dentre estes compostos, destacam-se as saponinas e seus metab?litos. Seu intenso uso ? decorrente de suas propriedades bioativas, somado a sua similaridade estrutural a horm?nios. As saponinas derivam-se em sapogeninas, como, por exemplo, a Diosgenina e a Hecogenina. Al?m de serem utilizadas na ind?stria farmac?utica para a produ??o de horm?nios e anti-inflamat?rios esteroidais, estas duas sapogeninas tamb?m s?o empregadas como fitoter?picos, estando presentes tamb?m em vegetais que comp?em a dieta de muitas popula??es. Apesar da vasta utiliza??o destes compostos, existe uma falta de informa??es sobre a toxicidade gen?tica, o que torna o consumo destas sapogeninas um risco para as popula??es. Diante deste contexto, o presente trabalho apresentou como objetivo investigar as potencialidades t?xicas, em n?vel celular e de DNA, da Diosgenina e da Hecogenina. Ensaios em c?lulas HepG2 para a avalia??o da citotoxicidade, genotoxicidade, e mutagenicidade foram realizados. Considerando os resultados obtidos com a Diosgenina, esta sapogenina revelou efeito citot?xico em concentra??es acima de 30 ?M, assim como induziu significativamente incrementos na frequ?ncia de danos no DNA e de micron?cleos. Por outro lado, a Hecogenina somente se revelou citot?xica acima de 150 ?M, por?m em concentra??es abaixo deste valor, foi capaz de induzir danos ao material gen?tico sem promover um aumento na frequ?ncia de micron?cleos. A an?lise do conjunto destes dados sugere que o consumo de alimentos, fitoter?picos ou de medicamentos que contenham a Diosgenina na sua composi??o apresenta um risco maior de toxicidade, quando comparados com as formula??es a base de Hecogenina, uma vez que a Diosgenina apresenta um potencial mutag?nico demonstrado por meio de um aumento significativo na frequ?ncia de micron?cleos que s?o biomarcadores de instabilidade gen?mica. === Natural products derived from plants are used as raw material for the synthesis of phytotherapeutics, and are widely used by many populations around the world. Among these compounds, there are the saponins and its metabolites. Its intense use is due to its bioactive properties, added to its structural similarity to hormones. Saponins derived in sapogenins, as Diosgenin and Hecogenin. Besides its use by pharmaceutical industries to synthesis of steroidal hormones and anti-inflammatories, these two sapogenins are also used as phytotherapeutics, being also present in vegetables from diets of many populations. Despite the widespread use of these compounds, there are a lack of information about their genetic toxicity, which makes the use of these sapogenins a risk. Given this context, the present work aimed to investigate the toxic potential of Diosgenin and Hecogenin, at cellular and DNA level. Assays with HepG2 cells was performed to evaluate the cytotoxicity, genotoxicity and mutagenicity. Considering the results obtained with Diosgenin, that sapogenin showed cytotoxic effects at concentrations higher than 30 ?M, as well as significantly induced increases in frequency of DNA damage and micronucleus. On the other hand, Hecogenin only revealed cytotoxicity above 150 ?M, however, at concentrations below this value, it was able to induce DNA damage without promote an increase in micronucleus frequency. The analysis of these results together suggests that the consumption of foods, phyotheraputics or medicines containing Diosgenin on its composition, presents a higher risk of toxicity when compared with formulations with Hecogenin, since Diosgenin shows a mutagenic potential demonstrated by a significant increase in micronucleus frequency, which are biomarkers of genome instability.