Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional 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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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). No. of bitstreams: 2 Dissertação - Aroldo Vieira de Moraes Filho - 2013.pdf: 777889 bytes, checksum: ff3a609fe7af52fcc55701fe96a8d450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2013-02-06Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Biologia (ICB)UFGBrasilInstituto de Ciências Biológicas - ICB (RG)Embargada pelo autor/orientador em 28/02/2013. Autorizado o povoamento pelo autor/orientador em 29/05/2017.6883982777473437920600600600600-3872772117827373404-55181442685852520512075167498588264571http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEfavirenzFumarato de tenofovir desoproxilaSMARTEfavirenzTenofovir disoproxil fumarateSMARTCIENCIAS BIOLOGICAS::GENETICAEstudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogasterGenetic toxicity study of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) in somatic cells of drosophila melanogasterinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://repositorio.bc.ufg.br/tede/bitstreams/8c54c5dd-4163-4c61-b03c-f17c714a81dc/downloadbd3efa91386c1718a7f26a329fdcb468MD51CC-LICENSElicense_urllicense_urltext/plain; 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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 |
dc.relation.department.fl_str_mv |
-3872772117827373404 |
dc.relation.cnpq.fl_str_mv |
-5518144268585252051 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Biologia (ICB) |
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 |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
instacron_str |
UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
http://repositorio.bc.ufg.br/tede/bitstreams/8c54c5dd-4163-4c61-b03c-f17c714a81dc/download http://repositorio.bc.ufg.br/tede/bitstreams/145c99f2-da34-4183-85cd-972c635bddd8/download http://repositorio.bc.ufg.br/tede/bitstreams/6129ee9a-f382-4421-9168-5b459ea47d89/download http://repositorio.bc.ufg.br/tede/bitstreams/caf6ae0b-4c0c-486d-a0dc-63e1d9b639c5/download http://repositorio.bc.ufg.br/tede/bitstreams/5963534a-78d1-41b5-8ee5-b3ba80c3addb/download |
bitstream.checksum.fl_str_mv |
bd3efa91386c1718a7f26a329fdcb468 4afdbb8c545fd630ea7db775da747b2f d41d8cd98f00b204e9800998ecf8427e d41d8cd98f00b204e9800998ecf8427e ff3a609fe7af52fcc55701fe96a8d450 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
_version_ |
1798044343023435776 |