Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster

Detalhes bibliográficos
Autor(a) principal: Moraes Filho, Aroldo Vieira de
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFG
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/7396
Resumo: The antiretroviral drugs appeared to prevent the multiplying HIV virus in the body, reducing its virulence, but not eliminate it from infected cells. These drugs increase the length and the quality of life of AIDS patients. In this context, Efavirenz (EFV) is non-nucleoside reverse transcriptase inhibitors. The Tenofovir Disoproxil Fumarate (TDF), oral prodrug of tenofovir, is analogue of adenosine 5 'monophosphate, belonging to the class of nucleotide reverse transcriptase inhibitors. These drugs act on the mechanisms of HIV replication by inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. In order to assess the toxic and toxic-genetic potential of EFV and TDF, the present study used the Test for Detection of Somatic Mutation and Recombination (SMART) in Drosophila melanogaster. 3rd stage larvae originating from standard cross (ST) between males mwh and females flr³, were treated with solution of EFV and TDF and distilled water (negative control), for approximately 48 hours (chronic treatment) until they reach the pupal stage. These strains are carriers of specific gene markers, located on the left arm of chromosome 3, which allow you to monitor events related to mutation, mitotic recombination and chromosome aberrations. The statistical diagnosis was obtained by conditional binomial test. In this work, the results demonstrated that the EFV was toxic in high concentrations, but showed no induction of toxic genetic events. Inversely, the TDF showed no toxicity at the concentrations tested, but was showed induction of toxic genetic events at all concentrations, with a prevalence of recombinogenic events. Then, it is essential to analyze constantly the effects risk/benefit of isolated drugs and identify toxic and toxic genetic activity of each drug in order to ensure the quality of life for patients who use monotherapies and offers support for investigations with therapies that use combinations of antiretroviral drugs.
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spelling Cunha, Kênya Silvahttp://lattes.cnpq.br/6124135410387685Cunha, Kênya Silvahttp://lattes.cnpq.br/6124135410387685Andrade, Heloisa Helena Rodrigues deChen, Lee ChenJesuino, Rosália Santos AmorimBataus, Luiz Artur Mendeshttp://lattes.cnpq.br/0642159645249357Moraes Filho, Aroldo Vieira de2017-06-01T11:20:14Z2013-02-06MORAES FILHO, A. V. Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster. 2013. 62 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.http://repositorio.bc.ufg.br/tede/handle/tede/7396The antiretroviral drugs appeared to prevent the multiplying HIV virus in the body, reducing its virulence, but not eliminate it from infected cells. These drugs increase the length and the quality of life of AIDS patients. In this context, Efavirenz (EFV) is non-nucleoside reverse transcriptase inhibitors. The Tenofovir Disoproxil Fumarate (TDF), oral prodrug of tenofovir, is analogue of adenosine 5 'monophosphate, belonging to the class of nucleotide reverse transcriptase inhibitors. These drugs act on the mechanisms of HIV replication by inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. In order to assess the toxic and toxic-genetic potential of EFV and TDF, the present study used the Test for Detection of Somatic Mutation and Recombination (SMART) in Drosophila melanogaster. 3rd stage larvae originating from standard cross (ST) between males mwh and females flr³, were treated with solution of EFV and TDF and distilled water (negative control), for approximately 48 hours (chronic treatment) until they reach the pupal stage. These strains are carriers of specific gene markers, located on the left arm of chromosome 3, which allow you to monitor events related to mutation, mitotic recombination and chromosome aberrations. The statistical diagnosis was obtained by conditional binomial test. In this work, the results demonstrated that the EFV was toxic in high concentrations, but showed no induction of toxic genetic events. Inversely, the TDF showed no toxicity at the concentrations tested, but was showed induction of toxic genetic events at all concentrations, with a prevalence of recombinogenic events. Then, it is essential to analyze constantly the effects risk/benefit of isolated drugs and identify toxic and toxic genetic activity of each drug in order to ensure the quality of life for patients who use monotherapies and offers support for investigations with therapies that use combinations of antiretroviral drugs.Os medicamentos antirretrovirais surgiram para impedir a multiplicação do vírus HIV no organismo, reduzindo a sua virulência, porém sem eliminá-lo das células infectadas. Estes medicamentos aumentaram o tempo e a qualidade de vida dos pacientes com AIDS. Dentro deste contexto, o Efavirenz (EFV) é inibidor da transcriptase reversa não-análogo de nucleosídeo. O Fumarato de Tenofovir Desoproxila (TDF), pró-fármaco oral de tenofovir, é análogo da adenosina 5`-monofosfato, pertencente à classe de inibidores da transcriptase reversa análogos de nucleotídeos. Estes fármacos atuam nos mecanismos de replicação do HIV, inibindo a ação da transcriptase reversa e, consequentemente, impedindo a síntese de DNA viral. Com o intuito de avaliar o potencial tóxico e tóxico genético do EFV e do TDF, utilizou-se o Teste para Detecção de Mutação e Recombinação Somática (SMART) em Drosophila melanogaster. Larvas de 3º estágio oriundas do Cruzamento Padrão (ST – standard cross) entre machos mwh e fêmeas flr³, foram tratadas com soluções de EFV e TDF, assim como com água destilada (controle negativo), por aproximadamente 48 h (tratamento crônico), isto é, até atingirem o estágio de pupa. Essas linhagens são portadoras de genes marcadores específicos, localizados no braço esquerdo do cromossomo 3, que permitem monitorar eventos relacionados com mutação gênica, aberrações cromossômicas e recombinação mitótica. O diagnóstico estatístico foi obtido pelo teste binomial condicional. Os resultados demonstraram que o EFV foi tóxico em altas concentrações, mas não induziu eventos tóxico genéticos. Inversamente, o TDF não apresentou toxicidade nas concentrações testadas, porém apresentou indução de efeitos tóxico genéticos em todas as concentrações, com prevalência dos eventos recombinogênicos. Então, torna-se fundamental analisar constantemente o risco/benefício de medicamentos isolados e identificar a atividade tóxica e tóxico-genética de cada fármaco com o intuito de assegurar qualidade de vida aos pacientes que fazem uso de monoterapias e oferecer suporte para as investigações com as terapias que utilizam combinações de antirretrovirais.Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-05-31T18:35:47Z No. of bitstreams: 2 Dissertação - Aroldo Vieira de Moraes Filho - 2013.pdf: 777889 bytes, checksum: ff3a609fe7af52fcc55701fe96a8d450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-06-01T11:20:13Z (GMT) No. of bitstreams: 2 Dissertação - Aroldo Vieira de Moraes Filho - 2013.pdf: 777889 bytes, checksum: ff3a609fe7af52fcc55701fe96a8d450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2017-06-01T11:20:14Z (GMT). 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dc.title.eng.fl_str_mv Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
dc.title.alternative.eng.fl_str_mv Genetic toxicity study of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) in somatic cells of drosophila melanogaster
title Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
spellingShingle Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
Moraes Filho, Aroldo Vieira de
Efavirenz
Fumarato de tenofovir desoproxila
SMART
Efavirenz
Tenofovir disoproxil fumarate
SMART
CIENCIAS BIOLOGICAS::GENETICA
title_short Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
title_full Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
title_fullStr Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
title_full_unstemmed Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
title_sort Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
author Moraes Filho, Aroldo Vieira de
author_facet Moraes Filho, Aroldo Vieira de
author_role author
dc.contributor.advisor1.fl_str_mv Cunha, Kênya Silva
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6124135410387685
dc.contributor.referee1.fl_str_mv Cunha, Kênya Silva
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/6124135410387685
dc.contributor.referee2.fl_str_mv Andrade, Heloisa Helena Rodrigues de
dc.contributor.referee3.fl_str_mv Chen, Lee Chen
dc.contributor.referee4.fl_str_mv Jesuino, Rosália Santos Amorim
dc.contributor.referee5.fl_str_mv Bataus, Luiz Artur Mendes
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0642159645249357
dc.contributor.author.fl_str_mv Moraes Filho, Aroldo Vieira de
contributor_str_mv Cunha, Kênya Silva
Cunha, Kênya Silva
Andrade, Heloisa Helena Rodrigues de
Chen, Lee Chen
Jesuino, Rosália Santos Amorim
Bataus, Luiz Artur Mendes
dc.subject.por.fl_str_mv Efavirenz
Fumarato de tenofovir desoproxila
SMART
topic Efavirenz
Fumarato de tenofovir desoproxila
SMART
Efavirenz
Tenofovir disoproxil fumarate
SMART
CIENCIAS BIOLOGICAS::GENETICA
dc.subject.eng.fl_str_mv Efavirenz
Tenofovir disoproxil fumarate
SMART
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::GENETICA
description The antiretroviral drugs appeared to prevent the multiplying HIV virus in the body, reducing its virulence, but not eliminate it from infected cells. These drugs increase the length and the quality of life of AIDS patients. In this context, Efavirenz (EFV) is non-nucleoside reverse transcriptase inhibitors. The Tenofovir Disoproxil Fumarate (TDF), oral prodrug of tenofovir, is analogue of adenosine 5 'monophosphate, belonging to the class of nucleotide reverse transcriptase inhibitors. These drugs act on the mechanisms of HIV replication by inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. In order to assess the toxic and toxic-genetic potential of EFV and TDF, the present study used the Test for Detection of Somatic Mutation and Recombination (SMART) in Drosophila melanogaster. 3rd stage larvae originating from standard cross (ST) between males mwh and females flr³, were treated with solution of EFV and TDF and distilled water (negative control), for approximately 48 hours (chronic treatment) until they reach the pupal stage. These strains are carriers of specific gene markers, located on the left arm of chromosome 3, which allow you to monitor events related to mutation, mitotic recombination and chromosome aberrations. The statistical diagnosis was obtained by conditional binomial test. In this work, the results demonstrated that the EFV was toxic in high concentrations, but showed no induction of toxic genetic events. Inversely, the TDF showed no toxicity at the concentrations tested, but was showed induction of toxic genetic events at all concentrations, with a prevalence of recombinogenic events. Then, it is essential to analyze constantly the effects risk/benefit of isolated drugs and identify toxic and toxic genetic activity of each drug in order to ensure the quality of life for patients who use monotherapies and offers support for investigations with therapies that use combinations of antiretroviral drugs.
publishDate 2013
dc.date.issued.fl_str_mv 2013-02-06
dc.date.accessioned.fl_str_mv 2017-06-01T11:20:14Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv MORAES FILHO, A. V. Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster. 2013. 62 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/7396
identifier_str_mv MORAES FILHO, A. V. Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster. 2013. 62 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.
url http://repositorio.bc.ufg.br/tede/handle/tede/7396
dc.language.iso.fl_str_mv por
language por
dc.relation.eng.fl_str_mv Embargada pelo autor/orientador em 28/02/2013. Autorizado o povoamento pelo autor/orientador em 29/05/2017.
dc.relation.program.fl_str_mv 6883982777473437920
dc.relation.confidence.fl_str_mv 600
600
600
600
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dc.publisher.none.fl_str_mv Universidade Federal de Goiás
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dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Ciências Biológicas - ICB (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFG - Universidade Federal de Goiás (UFG)
repository.mail.fl_str_mv tesesdissertacoes.bc@ufg.br ||tesesdissertacoes.bc@ufg.br
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