Efeitos da leucina no estresse oxidativo hepático e renal em ratos tratados com doxorrubicina

Detalhes bibliográficos
Autor(a) principal: Duarte, Poliana Rodrigues Alves
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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spelling 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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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
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instname_str Universidade Federal de Uberlândia (UFU)
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institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
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