Efeitos da leucina no estresse oxidativo hepático e renal em 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/123456789/21055 http://doi.org/10.14393/ufu.te.2017.168 |
Resumo: | Hepatic and renal toxicity is one of the side effects of doxorubicin used in the antineoplastic treatment. The aim of this study was to determine if leucine supplementation in the diet of Wistar rats treated with doxorubicin has protective hepatic and renal action evidenced by the reduction of oxidative stress. The experiment included 36 rats distributed in four groups, with 8 Control, 8 LEUcina, 10 DOXorubicin and 10 DOX + LEU. Animals from the DOX and DOX + LEU groups were treated with intraperitoneal injections of doxorubicin for two weeks, three times a week, at a cumulative dose of 7.5 mg / kg. The animals of groups C and LEU received intraperitoneal volume of saline daily, similar to that administered with doxorubicin. The LEU and DOX-LEU groups received the amino acid leucine throughout the study plus 5% added to the basal diet. Hepatic and renal tissue oxidative stress was evaluated by the dosages of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR) and also reduced levels of glutathione (GSH) and glucose-6-phosphate dehydrogenase (G6PDH); the oxidizing activity was measured by lipid peroxidation (thiobarbituric acid-TBARS). The hepatic collagen content was evaluated in histological analysis using picrosirius red staining; for analysis of the hepatic and renal tissues the Gomori trichrome was used. The results were presented as mean ± standard error of the mean (EPM), using GraphPad Prism software version 5.0. The results were compared by the Student's t-Test or the analysis of variance (ANOVA), as appropriate. To verify the detected differences between the groups, the Tukey test was used. Differences were considered significant when p <0.05. The results showed that, in the liver, the DOX group compared to the LEU presented higher antioxidant activity of SOD, catalase and Gpx, and GSH levels and lower levels of lipid peroxidation and collagen deposition. The group DOX + LEU compared to the LEU group also presented lower levels of lipid peroxidation and collagen deposition, and finally, the DOX + LEU group, when compared to the DOX group, presented lower oxidant activity and lower antioxidant activity of SOD, catalase, Gpx and GSH. The renal analyzes showed an increase in oxidative stress in the LEU group evidenced by the increase in GR. All experimental groups had a reduction in the total number of glomeruli in relation to the control. There was no change in collagen deposition. It was concluded that the addition of 5% leucine to the diet administered to doxorubicin treated rats showed a hepatoprotective effect. The hypothesis of leucine nephroprotective effect evidenced by the reduction of oxidative stress was not demonstrated. |
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Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicinaEffects of leucine on hepatic and renal oxidative stress in rats treated with doxorubicinCiências médicasDoxorrubicinaLeucinaStress oxidativoEstresse Oxidativo Hepático e RenalDoxorubicinLeucineOxidative stresshepatic and kidneyCNPQ::CIENCIAS DA SAUDE::MEDICINAHepatic and renal toxicity is one of the side effects of doxorubicin used in the antineoplastic treatment. The aim of this study was to determine if leucine supplementation in the diet of Wistar rats treated with doxorubicin has protective hepatic and renal action evidenced by the reduction of oxidative stress. The experiment included 36 rats distributed in four groups, with 8 Control, 8 LEUcina, 10 DOXorubicin and 10 DOX + LEU. Animals from the DOX and DOX + LEU groups were treated with intraperitoneal injections of doxorubicin for two weeks, three times a week, at a cumulative dose of 7.5 mg / kg. The animals of groups C and LEU received intraperitoneal volume of saline daily, similar to that administered with doxorubicin. The LEU and DOX-LEU groups received the amino acid leucine throughout the study plus 5% added to the basal diet. Hepatic and renal tissue oxidative stress was evaluated by the dosages of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR) and also reduced levels of glutathione (GSH) and glucose-6-phosphate dehydrogenase (G6PDH); the oxidizing activity was measured by lipid peroxidation (thiobarbituric acid-TBARS). The hepatic collagen content was evaluated in histological analysis using picrosirius red staining; for analysis of the hepatic and renal tissues the Gomori trichrome was used. The results were presented as mean ± standard error of the mean (EPM), using GraphPad Prism software version 5.0. The results were compared by the Student's t-Test or the analysis of variance (ANOVA), as appropriate. To verify the detected differences between the groups, the Tukey test was used. Differences were considered significant when p <0.05. The results showed that, in the liver, the DOX group compared to the LEU presented higher antioxidant activity of SOD, catalase and Gpx, and GSH levels and lower levels of lipid peroxidation and collagen deposition. The group DOX + LEU compared to the LEU group also presented lower levels of lipid peroxidation and collagen deposition, and finally, the DOX + LEU group, when compared to the DOX group, presented lower oxidant activity and lower antioxidant activity of SOD, catalase, Gpx and GSH. The renal analyzes showed an increase in oxidative stress in the LEU group evidenced by the increase in GR. All experimental groups had a reduction in the total number of glomeruli in relation to the control. There was no change in collagen deposition. It was concluded that the addition of 5% leucine to the diet administered to doxorubicin treated rats showed a hepatoprotective effect. The hypothesis of leucine nephroprotective effect evidenced by the reduction of oxidative stress was not demonstrated.Tese (Doutorado)A toxicidade hepática e renal é um dos efeitos colaterais da doxorrubicina utilizada no tratamento antineoplásico. O objetivo deste estudo foi determinar se a suplementação com leucina na dieta de ratos tratados com doxorrubicina tem ação protetora hepática e renal evidenciada pela redução do estresse oxidativo. O experimento incluiu 36 ratos distribuídos em quatro grupos sendo 8 Controles, 8 LEUcina, 10 DOXorrubicina e 10 DOX+LEU. Os animais dos grupos DOX e DOX+LEU foram tratados com injeções intraperitoneais de doxorrubicina durante duas semanas, três vezes por semana, atingindo-se a dose cumulativa de 7,5 mg/kg. Os animais dos grupos C e LEU receberam volume intraperitoneal de solução salina, diariamente, semelhante àquele administrado como veículo da a doxorrubicina. Os grupos LEU e DOX-LEU receberam o aminoácido leucina ao longo do estudo acrescido em 5% à dieta basal. O estresse oxidativo tecidual hepático e renal foi avaliado pelas dosagens das enzimas antioxidantes catalase, superóxido dismutase (SOD), glutationa peroxidase (Gpx), glutationa redutase (GR) e também dos níveis de glutationa reduzida (GSH) e glicose-6-fosfato desidrogenase (G6PDH); a atividade oxidante foi medida pela peroxidação lipídica (ácido tiobarbitúrico TBARS). O teor de colágeno hepático foi avaliado em análise histológica utilizando-se a coloração picrosirius red; para análise do tecido hepático e renal empregou-se a coloração pelo tricrômico de Gomori. Os resultados foram apresentados como média ± erro padrão da média (EPM). As diferenças foram consideradas significativas quando p<0,05. Os resultados mostraram que, no fígado, o grupo DOX comparado ao LEU apresentou aumento da atividade antioxidante de SOD, catalase e Gpx, e níveis de GSH e menores níveis de peroxidação lipídica e de deposição de colágeno. O grupo DOX+LEU comparado ao grupo LEU apresentou menores níveis de peroxidação lipídica e de deposição de colágeno e, finalmente, o grupo DOX +LEU, quando comparado ao grupo DOX, apresentou diminuição da atividade oxidante TBARS e da atividade antioxidante de SOD, catalase, Gpx e GSH. As análises renais mostraram um aumento do estresse oxidativo no grupo LEU evidenciado pelo aumento de GR. Todos os grupos experimentais apresentaram redução no número total de glomérulos em relação ao controle. Não houve alteração quanto à deposição de colágeno. Conclui-se que o acréscimo de 5% de leucina à dieta administrada aos ratos tratados com DOX mostrou efeito hepatoprotetor. A hipótese de efeito nefroprotetor da leucina evidenciado pela redução do estresse oxidativo, não foi demonstrada.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Ciências da SaúdeResende, Elmiro Santoshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4793244Y5Silva, Valdo José Diashttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723930Y1Celes, Mara Rubia Nuneshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702910Z2Pulici, Érica Carolina Camposhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133883H6Deconte, Simone Ramoshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4250533U5Duarte, Poliana Rodrigues Alves2018-04-03T18:45:29Z2018-04-03T18:45:29Z2017-08-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfDUARTE, Poliana Rodrigues Alves.Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina.2017.70 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.168 .https://repositorio.ufu.br/handle/123456789/21055http://doi.org/10.14393/ufu.te.2017.168porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2020-09-16T20:05:25Zoai:repositorio.ufu.br:123456789/21055Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2020-09-16T20:05:25Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.none.fl_str_mv |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina Effects of leucine on hepatic and renal oxidative stress in rats treated with doxorubicin |
title |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
spellingShingle |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina Duarte, Poliana Rodrigues Alves Ciências médicas Doxorrubicina Leucina Stress oxidativo Estresse Oxidativo Hepático e Renal Doxorubicin Leucine Oxidative stress hepatic and kidney CNPQ::CIENCIAS DA SAUDE::MEDICINA |
title_short |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
title_full |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
title_fullStr |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
title_full_unstemmed |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
title_sort |
Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina |
author |
Duarte, Poliana Rodrigues Alves |
author_facet |
Duarte, Poliana Rodrigues Alves |
author_role |
author |
dc.contributor.none.fl_str_mv |
Resende, Elmiro Santos http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4793244Y5 Silva, Valdo José Dias http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723930Y1 Celes, Mara Rubia Nunes http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702910Z2 Pulici, Érica Carolina Campos http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4133883H6 Deconte, Simone Ramos http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4250533U5 |
dc.contributor.author.fl_str_mv |
Duarte, Poliana Rodrigues Alves |
dc.subject.por.fl_str_mv |
Ciências médicas Doxorrubicina Leucina Stress oxidativo Estresse Oxidativo Hepático e Renal Doxorubicin Leucine Oxidative stress hepatic and kidney CNPQ::CIENCIAS DA SAUDE::MEDICINA |
topic |
Ciências médicas Doxorrubicina Leucina Stress oxidativo Estresse Oxidativo Hepático e Renal Doxorubicin Leucine Oxidative stress hepatic and kidney CNPQ::CIENCIAS DA SAUDE::MEDICINA |
description |
Hepatic and renal toxicity is one of the side effects of doxorubicin used in the antineoplastic treatment. The aim of this study was to determine if leucine supplementation in the diet of Wistar rats treated with doxorubicin has protective hepatic and renal action evidenced by the reduction of oxidative stress. The experiment included 36 rats distributed in four groups, with 8 Control, 8 LEUcina, 10 DOXorubicin and 10 DOX + LEU. Animals from the DOX and DOX + LEU groups were treated with intraperitoneal injections of doxorubicin for two weeks, three times a week, at a cumulative dose of 7.5 mg / kg. The animals of groups C and LEU received intraperitoneal volume of saline daily, similar to that administered with doxorubicin. The LEU and DOX-LEU groups received the amino acid leucine throughout the study plus 5% added to the basal diet. Hepatic and renal tissue oxidative stress was evaluated by the dosages of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR) and also reduced levels of glutathione (GSH) and glucose-6-phosphate dehydrogenase (G6PDH); the oxidizing activity was measured by lipid peroxidation (thiobarbituric acid-TBARS). The hepatic collagen content was evaluated in histological analysis using picrosirius red staining; for analysis of the hepatic and renal tissues the Gomori trichrome was used. The results were presented as mean ± standard error of the mean (EPM), using GraphPad Prism software version 5.0. The results were compared by the Student's t-Test or the analysis of variance (ANOVA), as appropriate. To verify the detected differences between the groups, the Tukey test was used. Differences were considered significant when p <0.05. The results showed that, in the liver, the DOX group compared to the LEU presented higher antioxidant activity of SOD, catalase and Gpx, and GSH levels and lower levels of lipid peroxidation and collagen deposition. The group DOX + LEU compared to the LEU group also presented lower levels of lipid peroxidation and collagen deposition, and finally, the DOX + LEU group, when compared to the DOX group, presented lower oxidant activity and lower antioxidant activity of SOD, catalase, Gpx and GSH. The renal analyzes showed an increase in oxidative stress in the LEU group evidenced by the increase in GR. All experimental groups had a reduction in the total number of glomeruli in relation to the control. There was no change in collagen deposition. It was concluded that the addition of 5% leucine to the diet administered to doxorubicin treated rats showed a hepatoprotective effect. The hypothesis of leucine nephroprotective effect evidenced by the reduction of oxidative stress was not demonstrated. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-08-04 2018-04-03T18:45:29Z 2018-04-03T18:45:29Z |
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 |
DUARTE, Poliana Rodrigues Alves.Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina.2017.70 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.168 . https://repositorio.ufu.br/handle/123456789/21055 http://doi.org/10.14393/ufu.te.2017.168 |
identifier_str_mv |
DUARTE, Poliana Rodrigues Alves.Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina.2017.70 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI http://doi.org/10.14393/ufu.te.2017.168 . |
url |
https://repositorio.ufu.br/handle/123456789/21055 http://doi.org/10.14393/ufu.te.2017.168 |
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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 |
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Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Ciências da Saúde |
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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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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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