Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFU |
Texto Completo: | https://repositorio.ufu.br/handle/123456789/21019 http://doi.org/10.14393/ufu.te.2017.177 |
Resumo: | Cardiotoxicity is one of the most significant adverse effects of oncologic treatment with doxorubicin being responsible for a high morbidity and mortality rate. These effects include the occurrence of cardiotoxicity that can lead to left ventricular dysfunction, heart failure and, ultimately, death. Studies have focused on the effects of leucine supplementation as a strategy to ameliorate and / or reverse the framework of proteolysis induced by various clinical complications. However, the impact of leucine supplementation on cardiotoxicity induced by doxorubicin is unknown. Objective: The objective of this study was to evaluate the effects of leucine supplementation on cardiotoxicity in rats treated with doxorubicin. Material and Methods: The experiment was carried out at the Center for Bioterism and Animal Experimentation (CEBEA-UFU) and lasted 42 days. Thirty-six male Wistar rats weighing between 250 and 300 grams were randomly assigned to four groups: Control (8 animals), Doxorubicin (10 animals), Leucine (8 animals) and Leucine + Doxorubicin (10 animals). Groups C and D received standard diet, while L and LD groups received leucine rich diet (supplemented in 5%). The animals of groups D and LD received intraperitoneal injections of doxorubicin three times a week over two weeks, reaching a cumulative dose of 7.5 mg / kg. Groups C and L received saline solution (NaCl 0.9%), intraperitoneally, in the same volume used for animals treated with doxorubicin. At the end of the experiment the animals were anesthetized and submitted to transthoracic echocardiography. At the end of experimental period cardiac collagen was quantified by histopathological study. For the comparisons between the groups, Student's t-Test or analysis of variance (ANOVA) was used, followed, by Tukey's test when necessary. Statistical significance was set at p <0.05. Results: In rats treated with a cumulative dose of 7.5 mg / kg doxorubicin, left ventricular (LV) dilation and decreased ejection fraction (LVEF) occurred. Leucine supplemented at 5% in the diet, prevented dilation and LV dysfunction when coadministered with doxorubicin. Changes in extracellular matrix remodeling were confirmed by the increase in collagen fibers in group D, which was attenuated when leucine supplementation occurred. There was a significant difference in the transverse diameter of the cardiomyocytes when the L, D and LD groups were compared with the C group, with the lower diameters found in the C group. Conclusion: Leucine attenuates cardiotoxicity in the experimental model of Wistar rats treated with doxorubicin and this effect is accompanied by maintenance of the collagen matrix. |
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Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicinaEffects of leucine supplementation on the heart of doxorubicin-treated ratsCiências médicasDoxorrubicinaCardiotoxidadeOncologiaAntraciclinasAminoácidoAnthracyclinesCardiotoxicityAmino AcidCNPQ::CIENCIAS DA SAUDE::MEDICINACardiotoxicity is one of the most significant adverse effects of oncologic treatment with doxorubicin being responsible for a high morbidity and mortality rate. These effects include the occurrence of cardiotoxicity that can lead to left ventricular dysfunction, heart failure and, ultimately, death. Studies have focused on the effects of leucine supplementation as a strategy to ameliorate and / or reverse the framework of proteolysis induced by various clinical complications. However, the impact of leucine supplementation on cardiotoxicity induced by doxorubicin is unknown. Objective: The objective of this study was to evaluate the effects of leucine supplementation on cardiotoxicity in rats treated with doxorubicin. Material and Methods: The experiment was carried out at the Center for Bioterism and Animal Experimentation (CEBEA-UFU) and lasted 42 days. Thirty-six male Wistar rats weighing between 250 and 300 grams were randomly assigned to four groups: Control (8 animals), Doxorubicin (10 animals), Leucine (8 animals) and Leucine + Doxorubicin (10 animals). Groups C and D received standard diet, while L and LD groups received leucine rich diet (supplemented in 5%). The animals of groups D and LD received intraperitoneal injections of doxorubicin three times a week over two weeks, reaching a cumulative dose of 7.5 mg / kg. Groups C and L received saline solution (NaCl 0.9%), intraperitoneally, in the same volume used for animals treated with doxorubicin. At the end of the experiment the animals were anesthetized and submitted to transthoracic echocardiography. At the end of experimental period cardiac collagen was quantified by histopathological study. For the comparisons between the groups, Student's t-Test or analysis of variance (ANOVA) was used, followed, by Tukey's test when necessary. Statistical significance was set at p <0.05. Results: In rats treated with a cumulative dose of 7.5 mg / kg doxorubicin, left ventricular (LV) dilation and decreased ejection fraction (LVEF) occurred. Leucine supplemented at 5% in the diet, prevented dilation and LV dysfunction when coadministered with doxorubicin. Changes in extracellular matrix remodeling were confirmed by the increase in collagen fibers in group D, which was attenuated when leucine supplementation occurred. There was a significant difference in the transverse diameter of the cardiomyocytes when the L, D and LD groups were compared with the C group, with the lower diameters found in the C group. Conclusion: Leucine attenuates cardiotoxicity in the experimental model of Wistar rats treated with doxorubicin and this effect is accompanied by maintenance of the collagen matrix.Tese (Doutorado)A cardiotoxicidade é um dos efeitos adversos mais significativos do tratamento oncológico com doxorrubicina sendo responsável por elevada taxa de morbimortalidade. Entre estes efeitos destaca-se a ocorrência de cardiotoxicidade que pode levar à disfunção ventricular esquerda, insuficiência cardíaca e, em última instância, à morte. Estudos têm focado os efeitos da suplementação de leucina como estratégia para amenizar e/ou reverter o quadro de proteólise induzido por diversos acometimentos clínicos. Contudo, desconhece-se o impacto da suplementação de leucina na cardiotoxicidade induzida pela doxorrubicina. Objetivo: O objetivo desse estudo foi avaliar os efeitos da suplementação de leucina na cardiotoxicidade em ratos tratados com doxorrubicina. Material e Métodos: O experimento foi realizado no Centro de Bioterismo e Experimentação Animal (CEBEA-UFU) e teve duração total de 42 dias. Foram utilizados 36 ratos Wistar, machos, com peso corporal entre 250 e 300 gramas, distribuídos aleatoriamente em quatro grupos, Controle (8 animais), Doxorrubicina (10 animais), Leucina (8 animais) e Leucina + Doxorrubicina (10 animais). Os Grupos C e D receberam dieta padrão, enquanto os grupos L e LD receberam dieta rica em leucina (suplementada em 5%). Os animais dos grupos D e LD , receberam injeções intraperitoneais de doxorrubicina, três vezes por semana, ao longo de duas semanas, atingindo-se a dose cumulativa de 7,5 mg/kg. Os grupos C e L receberam solução salina (soro fisiológico a 0,9%), via intraperitoneal, no mesmo volume empregado para os animais tratados com doxorrubicina. Ao final do experimento os animais foram anestesiados e submetidos à ecocardiografia transtorácica. Após a eutanásia, o colágeno cardíaco foi quantificado por estudo histopatológico. Para as comparações entre os grupos utilizou-se o Teste t de Student ou a análise de variância (ANOVA), seguida, quando necessário, pelo teste de Tukey. A significância estatística foi estabelecida para valores de p < 0,05. Resultados: Em ratos tratados com dose cumulativa de 7,5 mg/kg de doxorrubicina, ocorreu dilatação do ventrículo esquerdo (VE) e diminuição da fração de ejeção (FEVE). A leucina suplementada em 5% na ração preveniu a dilatação e a disfunção do VE quando coadministrada com doxorrubicina. Alterações no remodelamento da matriz extracelular foram confirmadas pelo aumento das fibras de colágeno no grupo D, efeito este atenuado quando houve suplementação de leucina. Houve diferença significante no diâmetro transversal dos cardiomiócitos quando se comparou os grupos L, D e LD, com o grupo C, sendo os menores diâmetros encontrados no grupo C. Conclusão: A leucina atenua a cardiotoxicidade no modelo experimental de ratos Wistar tratados com doxorrubicina e este efeito é acompanhado de manutenção da matriz de colágeno.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Ciências da SaúdeResende, Elmiro Santoshttp://lattes.cnpq.br/0155959835062402Antunes, Hanna Karen Moreirahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705662D5Marques, Cristhyano Pimentahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4526493Y7Pulici, Érica Camposhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133883H6Cheik , Nadia Carlahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4766082H6Fidale, Thiago Montes2018-03-28T19:34:58Z2018-03-28T19:34:58Z2017-08-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfFIDALE, Thiago Montes. Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina. 2017. 74 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.177https://repositorio.ufu.br/handle/123456789/21019http://doi.org/10.14393/ufu.te.2017.177porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2020-09-16T20:13:25Zoai:repositorio.ufu.br:123456789/21019Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2020-09-16T20:13:25Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.none.fl_str_mv |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina Effects of leucine supplementation on the heart of doxorubicin-treated rats |
title |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
spellingShingle |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina Fidale, Thiago Montes Ciências médicas Doxorrubicina Cardiotoxidade Oncologia Antraciclinas Aminoácido Anthracyclines Cardiotoxicity Amino Acid CNPQ::CIENCIAS DA SAUDE::MEDICINA |
title_short |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
title_full |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
title_fullStr |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
title_full_unstemmed |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
title_sort |
Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina |
author |
Fidale, Thiago Montes |
author_facet |
Fidale, Thiago Montes |
author_role |
author |
dc.contributor.none.fl_str_mv |
Resende, Elmiro Santos http://lattes.cnpq.br/0155959835062402 Antunes, Hanna Karen Moreira http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705662D5 Marques, Cristhyano Pimenta http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4526493Y7 Pulici, Érica Campos http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133883H6 Cheik , Nadia Carla http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4766082H6 |
dc.contributor.author.fl_str_mv |
Fidale, Thiago Montes |
dc.subject.por.fl_str_mv |
Ciências médicas Doxorrubicina Cardiotoxidade Oncologia Antraciclinas Aminoácido Anthracyclines Cardiotoxicity Amino Acid CNPQ::CIENCIAS DA SAUDE::MEDICINA |
topic |
Ciências médicas Doxorrubicina Cardiotoxidade Oncologia Antraciclinas Aminoácido Anthracyclines Cardiotoxicity Amino Acid CNPQ::CIENCIAS DA SAUDE::MEDICINA |
description |
Cardiotoxicity is one of the most significant adverse effects of oncologic treatment with doxorubicin being responsible for a high morbidity and mortality rate. These effects include the occurrence of cardiotoxicity that can lead to left ventricular dysfunction, heart failure and, ultimately, death. Studies have focused on the effects of leucine supplementation as a strategy to ameliorate and / or reverse the framework of proteolysis induced by various clinical complications. However, the impact of leucine supplementation on cardiotoxicity induced by doxorubicin is unknown. Objective: The objective of this study was to evaluate the effects of leucine supplementation on cardiotoxicity in rats treated with doxorubicin. Material and Methods: The experiment was carried out at the Center for Bioterism and Animal Experimentation (CEBEA-UFU) and lasted 42 days. Thirty-six male Wistar rats weighing between 250 and 300 grams were randomly assigned to four groups: Control (8 animals), Doxorubicin (10 animals), Leucine (8 animals) and Leucine + Doxorubicin (10 animals). Groups C and D received standard diet, while L and LD groups received leucine rich diet (supplemented in 5%). The animals of groups D and LD received intraperitoneal injections of doxorubicin three times a week over two weeks, reaching a cumulative dose of 7.5 mg / kg. Groups C and L received saline solution (NaCl 0.9%), intraperitoneally, in the same volume used for animals treated with doxorubicin. At the end of the experiment the animals were anesthetized and submitted to transthoracic echocardiography. At the end of experimental period cardiac collagen was quantified by histopathological study. For the comparisons between the groups, Student's t-Test or analysis of variance (ANOVA) was used, followed, by Tukey's test when necessary. Statistical significance was set at p <0.05. Results: In rats treated with a cumulative dose of 7.5 mg / kg doxorubicin, left ventricular (LV) dilation and decreased ejection fraction (LVEF) occurred. Leucine supplemented at 5% in the diet, prevented dilation and LV dysfunction when coadministered with doxorubicin. Changes in extracellular matrix remodeling were confirmed by the increase in collagen fibers in group D, which was attenuated when leucine supplementation occurred. There was a significant difference in the transverse diameter of the cardiomyocytes when the L, D and LD groups were compared with the C group, with the lower diameters found in the C group. Conclusion: Leucine attenuates cardiotoxicity in the experimental model of Wistar rats treated with doxorubicin and this effect is accompanied by maintenance of the collagen matrix. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08-30 2018-03-28T19:34:58Z 2018-03-28T19:34:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
FIDALE, Thiago Montes. Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina. 2017. 74 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.177 https://repositorio.ufu.br/handle/123456789/21019 http://doi.org/10.14393/ufu.te.2017.177 |
identifier_str_mv |
FIDALE, Thiago Montes. Efeitos da suplementação de leucina no coração de ratos tratados com doxorrubicina. 2017. 74 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.177 |
url |
https://repositorio.ufu.br/handle/123456789/21019 http://doi.org/10.14393/ufu.te.2017.177 |
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por |
language |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Ciências da Saúde |
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reponame:Repositório Institucional da UFU instname:Universidade Federal de Uberlândia (UFU) instacron:UFU |
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Universidade Federal de Uberlândia (UFU) |
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UFU |
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Repositório Institucional da UFU |
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Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU) |
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diinf@dirbi.ufu.br |
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