Efeito da quercetina sobre a hiperglicemia induzida pelo tamoxifeno em ratas ovariectomizadas

Detalhes bibliográficos
Autor(a) principal: Silva, Fernanda Coleraus
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/624
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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spelling Itinose, Ana MariaCPF:23538392900http://lattes.cnpq.br/0536964833084241Marek, Carla BruginCPF:75271257991http://lattes.cnpq.br/2802989594048763Baroni, SilmaraCPF:03710644909http://lattes.cnpq.br/5828140324071034http://lattes.cnpq.br/2232621893539470Silva, Fernanda Coleraus2017-07-10T13:59:28Z2016-04-182015-12-07SILVA, 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/624Tamoxifen 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 2017-07-10T13:59:28Z (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/624/1/EFEITO+DA+QUERCETINA+OVARIECTOMIZADAS.pdfae46af8ec18f6634ae18e23c19f6e393MD51tede/6242017-10-20 11:01:48.721oai:tede.unioeste.br:tede/624Biblioteca Digital de Teses e Dissertaçõeshttp://tede.unioeste.br/PUBhttp://tede.unioeste.br/oai/requestbiblioteca.repositorio@unioeste.bropendoar:2017-10-20T13:01:48Biblioteca 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.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 2017-07-10T13:59:28Z
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/624
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.
url http://tede.unioeste.br:8080/tede/handle/tede/624
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dc.publisher.none.fl_str_mv Universidade Estadual do Oeste do Parana
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dc.publisher.department.fl_str_mv Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade Estadual do Oeste do Parana
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