Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UNIOESTE |
Texto Completo: | http://tede.unioeste.br:8080/tede/handle/tede/9 |
Resumo: | Tamoxifen was discovered in 1970 and classified as selective estrogen receptor modulator (SERM) being used as therapy in the treatment of breast cancer. Although benefits has been proven, side effects are intense, and are related to different mechanisms of toxic action, such as oxidative stress and changes in the glycolytic pathway that induce a hyperglycemia and liver damage. The administration of quercetin, a flavonoid with antioxidant potential, that has inhibitory effect on enzyme butyrylcholinesterase, an enzyme possibly associated with hepatotoxicity and hyperglycemia, has benefits on the adverse effects caused by tamoxifen. Thus, first to determine the effect of quercetin on the hyperglycemia caused by tamoxifen, ovariectomized rats were treated orally, with tamoxifen and quercetin; concluding that effects of quercetin are dependent on ratio quercetin/tamoxifen coadministered and the 4.5 ratio is more effective. After, trying to elucidate the mechanisms involved in changes in the glycolytic pathway, oxidative stress and liver damage perfusion was performed in rat liver, studying especially glycogenolysis and gluconeogenesis, using as an indicator of liver damage of butyrylcholinesterase activity and monitoring the oxidative stress. The results showed that quercetin has inhibitory effect on glucose production and enhances the effects generated by tamoxifen in gluconeogenesis, concluding that although quercetin is known for antioxidant activity, in certain concentrations (400 μM) intensifies the damage initially caused by tamoxifen, this effect doesn't occur with lower concentrations of quercetin (200 μM). Therefore, although quercetin has shown to be effective in reducing hyperglycemia caused by tamoxifen, the interaction of quercetin with tamoxifen should be viewed with caution since the effect of this interaction in carbohydrate metabolism is intense, can alter the intracellular redox environment, compromising its integrity and causing serious damage to liver tissue. |
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Itinose, Ana MariaCPF:23538392900http://lattes.cnpq.br/0536964833084241Marek, Carla BruginCPF:75271257991http://lattes.cnpq.br/2802989594048763Baroni, SilmaraCPF:03710644909http://lattes.cnpq.br/5828140324071034CPF:05911134900http://lattes.cnpq.br/2232621893539470Silva, Fernanda Coleraus2017-05-12T14:36:24Z2016-04-182015-12-07SILVA, Fernanda Coleraus. Effect of quercetin in hyperglycemia induced by tamoxifen in ovariectomized rats. 2015. 135 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Parana, Cascavel, 2015.http://tede.unioeste.br:8080/tede/handle/tede/9Tamoxifen was discovered in 1970 and classified as selective estrogen receptor modulator (SERM) being used as therapy in the treatment of breast cancer. Although benefits has been proven, side effects are intense, and are related to different mechanisms of toxic action, such as oxidative stress and changes in the glycolytic pathway that induce a hyperglycemia and liver damage. The administration of quercetin, a flavonoid with antioxidant potential, that has inhibitory effect on enzyme butyrylcholinesterase, an enzyme possibly associated with hepatotoxicity and hyperglycemia, has benefits on the adverse effects caused by tamoxifen. Thus, first to determine the effect of quercetin on the hyperglycemia caused by tamoxifen, ovariectomized rats were treated orally, with tamoxifen and quercetin; concluding that effects of quercetin are dependent on ratio quercetin/tamoxifen coadministered and the 4.5 ratio is more effective. After, trying to elucidate the mechanisms involved in changes in the glycolytic pathway, oxidative stress and liver damage perfusion was performed in rat liver, studying especially glycogenolysis and gluconeogenesis, using as an indicator of liver damage of butyrylcholinesterase activity and monitoring the oxidative stress. The results showed that quercetin has inhibitory effect on glucose production and enhances the effects generated by tamoxifen in gluconeogenesis, concluding that although quercetin is known for antioxidant activity, in certain concentrations (400 μM) intensifies the damage initially caused by tamoxifen, this effect doesn't occur with lower concentrations of quercetin (200 μM). Therefore, although quercetin has shown to be effective in reducing hyperglycemia caused by tamoxifen, the interaction of quercetin with tamoxifen should be viewed with caution since the effect of this interaction in carbohydrate metabolism is intense, can alter the intracellular redox environment, compromising its integrity and causing serious damage to liver tissue.O tamoxifeno, descoberto em 1970 foi classificado como modulador seletivo de receptor de estrógeno (SERM) sendo utilizado no tramento e prevenção do câncer de mama e embora seja terapia de escolha no período pós-menopausa seus efeitos colaterais são intensos, e estão relacionados a diferentes mecanismos de ação tóxica, como o estresse oxidativo e alterações na via glicolítica que induzem a hiperglicemia e causam danos hepáticos. A coadministração de quercetina, um flavonoide com potencial antioxidante e que possui efeito inibitório na enzima butirilcolinesterase, enzima essa possivelmente associada a hepatotoxicidade e a hiperglicemia, traria benefícios diante dos efeitos adversos gerados pelo tamoxifeno. Sendo assim, primeiramente, para determinar o efeito da quercetina diante da hiperglicemia causada pelo tamoxifeno, ratas ovariectomizadas foram tratadas via oral com quercetina e tamoxifeno; concluindo que os efeitos da quercetina são dependentes da razão Quercetina/Tamoxifeno coadministrado, e na razão 4,5 a quercetina mostra-se altamentente eficaz. Após, buscando elucidar os mecanismos envolvidos nas alterações na via glicolítica, os danos hepáticos e o estresse oxidativo, foram realizados perfusão em fígado isolado de ratas, estudando em especial a glicogenólise e a gliconeogênese, utilizando como indicador dos danos hepáticos a atividade da butirilcolinesterase e monitorando o estresse oxidativo. Os resultados mostraram que a quercetina possui efeito inibitório (200 μM) sobre a produção de glicose e intensifica os efeitos gerados pelo tamoxifeno na gliconeogênese, concluindo que embora a quercetina seja reconhecida pela sua atividade antioxidante, em determinadas concentrações (400 μM) ela acentua os danos inicialmente causados pelo tamoxifeno, não ocorrendo esse efeito com concentrações mais baixas de quercetina (200 μM). Sendo assim, embora a quercetina tenha se mostrado eficaz, reduzindo a hiperglicemia causada pelo tamoxifeno via oral, a interação da quercetina com tamoxifeno deve ser vista com cautela, pois os resultados mostram que o efeito dessa interação no metabolismo de carboidratos é intenso, podendo alterar o ambiente redox intracelular, comprometer a integridade celular e causar danos graves no tecido hepático.Made available in DSpace on 2017-05-12T14:36:24Z (GMT). No. of bitstreams: 1 EFEITO DA QUERCETINA OVARIECTOMIZADAS.pdf: 2103814 bytes, checksum: ae46af8ec18f6634ae18e23c19f6e393 (MD5) Previous issue date: 2015-12-07application/pdfporUniversidade Estadual do Oeste do ParanaPrograma de Pós-Graduação em Ciências Farmacêuticas MestradoUNIOESTEBRCiências FarmacêuticasButirilcolinesteraseEstresse oxidativoSERMFlavonoidesButyrylcholinesteraseOxidative stressSERMFlavonoidsCNPQ::CIENCIAS DA SAUDE::FARMACIAEfeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadasEffect of quercetin in hyperglycemia induced by tamoxifen in ovariectomized ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UNIOESTEinstname:Universidade Estadual do Oeste do Paraná (UNIOESTE)instacron:UNIOESTEORIGINALEFEITO DA QUERCETINA OVARIECTOMIZADAS.pdfapplication/pdf2103814http://tede.unioeste.br:8080/tede/bitstream/tede/9/1/EFEITO+DA+QUERCETINA+OVARIECTOMIZADAS.pdfae46af8ec18f6634ae18e23c19f6e393MD51tede/92017-05-12 11:36:25.001oai:tede.unioeste.br:tede/9Biblioteca Digital de Teses e Dissertaçõeshttp://tede.unioeste.br/PUBhttp://tede.unioeste.br/oai/requestbiblioteca.repositorio@unioeste.bropendoar:2017-05-12T14:36:25Biblioteca Digital de Teses e Dissertações do UNIOESTE - Universidade Estadual do Oeste do Paraná (UNIOESTE)false |
dc.title.por.fl_str_mv |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
dc.title.alternative.eng.fl_str_mv |
Effect of quercetin in hyperglycemia induced by tamoxifen in ovariectomized rats |
title |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
spellingShingle |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas Silva, Fernanda Coleraus Butirilcolinesterase Estresse oxidativo SERM Flavonoides Butyrylcholinesterase Oxidative stress SERM Flavonoids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
title_full |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
title_fullStr |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
title_full_unstemmed |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
title_sort |
Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas |
author |
Silva, Fernanda Coleraus |
author_facet |
Silva, Fernanda Coleraus |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Itinose, Ana Maria |
dc.contributor.advisor1ID.fl_str_mv |
CPF:23538392900 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0536964833084241 |
dc.contributor.referee1.fl_str_mv |
Marek, Carla Brugin |
dc.contributor.referee1ID.fl_str_mv |
CPF:75271257991 |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2802989594048763 |
dc.contributor.referee2.fl_str_mv |
Baroni, Silmara |
dc.contributor.referee2ID.fl_str_mv |
CPF:03710644909 |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5828140324071034 |
dc.contributor.authorID.fl_str_mv |
CPF:05911134900 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2232621893539470 |
dc.contributor.author.fl_str_mv |
Silva, Fernanda Coleraus |
contributor_str_mv |
Itinose, Ana Maria Marek, Carla Brugin Baroni, Silmara |
dc.subject.por.fl_str_mv |
Butirilcolinesterase Estresse oxidativo SERM Flavonoides |
topic |
Butirilcolinesterase Estresse oxidativo SERM Flavonoides Butyrylcholinesterase Oxidative stress SERM Flavonoids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Butyrylcholinesterase Oxidative stress SERM Flavonoids |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Tamoxifen was discovered in 1970 and classified as selective estrogen receptor modulator (SERM) being used as therapy in the treatment of breast cancer. Although benefits has been proven, side effects are intense, and are related to different mechanisms of toxic action, such as oxidative stress and changes in the glycolytic pathway that induce a hyperglycemia and liver damage. The administration of quercetin, a flavonoid with antioxidant potential, that has inhibitory effect on enzyme butyrylcholinesterase, an enzyme possibly associated with hepatotoxicity and hyperglycemia, has benefits on the adverse effects caused by tamoxifen. Thus, first to determine the effect of quercetin on the hyperglycemia caused by tamoxifen, ovariectomized rats were treated orally, with tamoxifen and quercetin; concluding that effects of quercetin are dependent on ratio quercetin/tamoxifen coadministered and the 4.5 ratio is more effective. After, trying to elucidate the mechanisms involved in changes in the glycolytic pathway, oxidative stress and liver damage perfusion was performed in rat liver, studying especially glycogenolysis and gluconeogenesis, using as an indicator of liver damage of butyrylcholinesterase activity and monitoring the oxidative stress. The results showed that quercetin has inhibitory effect on glucose production and enhances the effects generated by tamoxifen in gluconeogenesis, concluding that although quercetin is known for antioxidant activity, in certain concentrations (400 μM) intensifies the damage initially caused by tamoxifen, this effect doesn't occur with lower concentrations of quercetin (200 μM). Therefore, although quercetin has shown to be effective in reducing hyperglycemia caused by tamoxifen, the interaction of quercetin with tamoxifen should be viewed with caution since the effect of this interaction in carbohydrate metabolism is intense, can alter the intracellular redox environment, compromising its integrity and causing serious damage to liver tissue. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-12-07 |
dc.date.available.fl_str_mv |
2016-04-18 |
dc.date.accessioned.fl_str_mv |
2017-05-12T14:36:24Z |
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 |
SILVA, Fernanda Coleraus. Effect of quercetin in hyperglycemia induced by tamoxifen in ovariectomized rats. 2015. 135 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Parana, Cascavel, 2015. |
dc.identifier.uri.fl_str_mv |
http://tede.unioeste.br:8080/tede/handle/tede/9 |
identifier_str_mv |
SILVA, Fernanda Coleraus. Effect of quercetin in hyperglycemia induced by tamoxifen in ovariectomized rats. 2015. 135 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Parana, Cascavel, 2015. |
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http://tede.unioeste.br:8080/tede/handle/tede/9 |
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por |
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por |
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openAccess |
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Universidade Estadual do Oeste do Parana |
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Programa de Pós-Graduação em Ciências Farmacêuticas Mestrado |
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UNIOESTE |
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BR |
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Ciências Farmacêuticas |
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Universidade Estadual do Oeste do Parana |
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