Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica

Detalhes bibliográficos
Autor(a) principal: Nepomuceno, Leilane Maria Barcellos
Data de Publicação: 2013
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/12313
Resumo: Radiotherapy is often used to treat prostate tumors, but the normal bladder is usually adversely affected. Using an animal model of pelvic radiation, we investigated whether glutamine nutritional supplementation can prevent radiation-induced damage to the bladder, especially in its more superficial layers. Male rats aged 3 to 4 months were divided into groups of 8 animals each: controls, which consisted intact animals; radiated-only rats, which were sacrificed 7 (R7) or 15 (R15) days after a radiation session (10 Gy aimed at the pelvico-abdominal region); and radiated rats receiving L-glutamine supplementation (0.65 g/kg body weight/day), which were sacrificed 7 (RG7) or 15 (RG15) days after the radiation session. Morphological and morphometric analysis of the urothelium were made. Nuclear density, lamina propria cell density and mast cells numbers per area were counted. The results showed that, in R7, epithelial thickness, epithelial cell density, and cell density in the lamina propria were not significantly affected. However, density of blood vessels in R7 was reduced by 48% (p < 0.05) and this alteration was mostly prevented by glutamine (p < 0.02). In R15, density of blood vessels in the lamina propria was not significantly modified. However, epithelial thickness was reduced by 25% (p < 0.05) in R15, and this effect was prevented by glutamine (p < 0.01). In R15, epithelial cell density was increased by 35% (p < 0.02), but glutamine did not protect against this radiation-induced increase. Cell density in the lamina propria was likewise unaffected in R15. Density of mast cells in the lamina propria was markedly reduced in R7 and R15. The density was still reduced in RG7, but a higher density in RG15 suggested a glutamine-mediated recovery. Alpha-actin positive cells in the lamina propria formed a suburothelial layer and were identified as myofibroblasts. Thickness of this layer was increased in R7, but was similar to controls in RG7, while changes in R15 and RG15 were less evident. In conclusion, pelvic radiation leads to significant acute and post-acute alterations in the composition and structural features of the vesical lamina propria and epithelium. Most of these changes, however, can be prevented by glutamine nutritional supplementation. These results emphasize, therefore, the potential use of this aminoacid as a radioprotective drug.
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spelling Sampaio, Francisco José Barcelloshttp://lattes.cnpq.br/4426830285523015Costa, Waldemar Silvahttp://lattes.cnpq.br/6986274610951714Souza, Diogo Benchimol dehttp://lattes.cnpq.br/2970551390843240Bastos, Ana Luizahttp://lattes.cnpq.br/9675718849586180Chagas, Maurício Alveshttp://lattes.cnpq.br/9509972220597549Sampaio, Marco Aurélio Pereirahttp://lattes.cnpq.br/2974617010463918http://lattes.cnpq.br/6262205349813599Nepomuceno, Leilane Maria Barcellos2021-01-06T20:31:54Z2013-11-012013-04-17NEPOMUCENO, Leilane Maria Barcellos. Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica. 2013. 71 f. Tese (Doutorado em Sistema Urogenital; Sistema Cardiovascular; Técnica operatória e Cirurgia Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.http://www.bdtd.uerj.br/handle/1/12313Radiotherapy is often used to treat prostate tumors, but the normal bladder is usually adversely affected. Using an animal model of pelvic radiation, we investigated whether glutamine nutritional supplementation can prevent radiation-induced damage to the bladder, especially in its more superficial layers. Male rats aged 3 to 4 months were divided into groups of 8 animals each: controls, which consisted intact animals; radiated-only rats, which were sacrificed 7 (R7) or 15 (R15) days after a radiation session (10 Gy aimed at the pelvico-abdominal region); and radiated rats receiving L-glutamine supplementation (0.65 g/kg body weight/day), which were sacrificed 7 (RG7) or 15 (RG15) days after the radiation session. Morphological and morphometric analysis of the urothelium were made. Nuclear density, lamina propria cell density and mast cells numbers per area were counted. The results showed that, in R7, epithelial thickness, epithelial cell density, and cell density in the lamina propria were not significantly affected. However, density of blood vessels in R7 was reduced by 48% (p < 0.05) and this alteration was mostly prevented by glutamine (p < 0.02). In R15, density of blood vessels in the lamina propria was not significantly modified. However, epithelial thickness was reduced by 25% (p < 0.05) in R15, and this effect was prevented by glutamine (p < 0.01). In R15, epithelial cell density was increased by 35% (p < 0.02), but glutamine did not protect against this radiation-induced increase. Cell density in the lamina propria was likewise unaffected in R15. Density of mast cells in the lamina propria was markedly reduced in R7 and R15. The density was still reduced in RG7, but a higher density in RG15 suggested a glutamine-mediated recovery. Alpha-actin positive cells in the lamina propria formed a suburothelial layer and were identified as myofibroblasts. Thickness of this layer was increased in R7, but was similar to controls in RG7, while changes in R15 and RG15 were less evident. In conclusion, pelvic radiation leads to significant acute and post-acute alterations in the composition and structural features of the vesical lamina propria and epithelium. Most of these changes, however, can be prevented by glutamine nutritional supplementation. These results emphasize, therefore, the potential use of this aminoacid as a radioprotective drug.A radioterapia é frequentemente utilizada no tratamento de tumores da próstata, porém durante esse procedimento a bexiga sadia usualmente sofre efeitos colaterais. Através do uso de um modelo animal para irradiação pélvica, avaliamos se a suplementação nutricional com L-glutamina poderia prevenir possíveis danos na parede da bexiga, especialmente em suas camadas mais superficiais. Ratos Wistar adultos machos com idade entre 3 e 4 meses foram separados em grupos de 8 animais: grupo controle que não recebeu a irradiação; grupos somente irradiados que foram mortos 7 (R7) e 15 dias (R15) após a irradiação (dose única de 10 Gy na região pélvico-abdominal); grupos irradiados e suplementados com L-glutamina (0,65g/kg de peso por dia), que foram mortos 7 (RG7) ou 15 após a irradiação. Células e vasos sanguíneos da lâmina própria, bem como o urotélio, foram avaliados com métodos histológicos. No urotélio foram feitas análises da altura e densidade nuclear e na lâmina própria densidade celular, densidade vascular e o número de mastócitos. Os resultados mostraram que em R7, a altura e densidade nuclear do urotélio e a densidade celular da lâmina própria não foram alterados significativamente. Entretanto a densidade dos vasos sanguíneos foi reduzida em 48% (p<0,05) e essa alteração foi evitada pela glutamina (p <0,02). No grupo R15, a densidade celular do epitélio aumentou em 35% (p<0,02). A densidade celular da lâmina própria não apresentou diferença estatística entre os grupos. Os mastócitos na lâmina própria foram reduzidos em R7 e R15. Apesar de ainda reduzidos em RG7 em RG15 houve aumento no número desse tipo celular o que sugere uma ação positiva da glutamina. Células α-actina positivas na lâmina própria formam uma camada suburotelial e foram identificadas como miofibroblastos. A espessura dessa camada aumentou em R7, mas foi semelhante ao controle em RG7, enquanto alterações em R15 e RG15 foram menos evidentes. Esses resultados mostraram que a utilização da L-glutamina antes e após a radioterapia deve ser considerada para uso humano na proteção da bexiga contra os efeitos da radiação.Submitted by Boris Flegr (boris@uerj.br) on 2021-01-06T20:31:54Z No. of bitstreams: 1 TESE_FINAL_Leilane_Maria_Barcellos_Nepomuceno_Reduzido.pdf: 9398883 bytes, checksum: c192e799e5eb46ebf3642f86b09794f6 (MD5)Made available in DSpace on 2021-01-06T20:31:54Z (GMT). No. of bitstreams: 1 TESE_FINAL_Leilane_Maria_Barcellos_Nepomuceno_Reduzido.pdf: 9398883 bytes, checksum: c192e799e5eb46ebf3642f86b09794f6 (MD5) Previous issue date: 2013-04-17application/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Fisiopatologia e Ciências CirúrgicasUERJBRCentro Biomédico::Faculdade de Ciências MédicasUrinary bladderGlutamineMyofibroblastsRadiotherapyBexiga urináriaGlutaminaMiofibroblastosRadioterapiaRadioterapiaGlutaminaBexigaEfeito da radiaçãoCNPQ::CIENCIAS DA SAUDE::MEDICINAEfeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvicaProtective effects of L-Glutamine on the bladder wall of rats submitted to pelvic radiationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALTESE_FINAL_Leilane_Maria_Barcellos_Nepomuceno_Reduzido.pdfapplication/pdf9398883http://www.bdtd.uerj.br/bitstream/1/12313/1/TESE_FINAL_Leilane_Maria_Barcellos_Nepomuceno_Reduzido.pdfc192e799e5eb46ebf3642f86b09794f6MD511/123132024-02-26 16:45:33.404oai:www.bdtd.uerj.br:1/12313Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T19:45:33Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
dc.title.alternative.eng.fl_str_mv Protective effects of L-Glutamine on the bladder wall of rats submitted to pelvic radiation
title Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
spellingShingle Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
Nepomuceno, Leilane Maria Barcellos
Urinary bladder
Glutamine
Myofibroblasts
Radiotherapy
Bexiga urinária
Glutamina
Miofibroblastos
Radioterapia
Radioterapia
Glutamina
Bexiga
Efeito da radiação
CNPQ::CIENCIAS DA SAUDE::MEDICINA
title_short Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
title_full Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
title_fullStr Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
title_full_unstemmed Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
title_sort Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica
author Nepomuceno, Leilane Maria Barcellos
author_facet Nepomuceno, Leilane Maria Barcellos
author_role author
dc.contributor.advisor1.fl_str_mv Sampaio, Francisco José Barcellos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4426830285523015
dc.contributor.advisor-co1.fl_str_mv Costa, Waldemar Silva
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/6986274610951714
dc.contributor.referee1.fl_str_mv Souza, Diogo Benchimol de
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/2970551390843240
dc.contributor.referee2.fl_str_mv Bastos, Ana Luiza
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/9675718849586180
dc.contributor.referee3.fl_str_mv Chagas, Maurício Alves
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/9509972220597549
dc.contributor.referee4.fl_str_mv Sampaio, Marco Aurélio Pereira
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/2974617010463918
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6262205349813599
dc.contributor.author.fl_str_mv Nepomuceno, Leilane Maria Barcellos
contributor_str_mv Sampaio, Francisco José Barcellos
Costa, Waldemar Silva
Souza, Diogo Benchimol de
Bastos, Ana Luiza
Chagas, Maurício Alves
Sampaio, Marco Aurélio Pereira
dc.subject.eng.fl_str_mv Urinary bladder
Glutamine
Myofibroblasts
Radiotherapy
topic Urinary bladder
Glutamine
Myofibroblasts
Radiotherapy
Bexiga urinária
Glutamina
Miofibroblastos
Radioterapia
Radioterapia
Glutamina
Bexiga
Efeito da radiação
CNPQ::CIENCIAS DA SAUDE::MEDICINA
dc.subject.por.fl_str_mv Bexiga urinária
Glutamina
Miofibroblastos
Radioterapia
Radioterapia
Glutamina
Bexiga
Efeito da radiação
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
description Radiotherapy is often used to treat prostate tumors, but the normal bladder is usually adversely affected. Using an animal model of pelvic radiation, we investigated whether glutamine nutritional supplementation can prevent radiation-induced damage to the bladder, especially in its more superficial layers. Male rats aged 3 to 4 months were divided into groups of 8 animals each: controls, which consisted intact animals; radiated-only rats, which were sacrificed 7 (R7) or 15 (R15) days after a radiation session (10 Gy aimed at the pelvico-abdominal region); and radiated rats receiving L-glutamine supplementation (0.65 g/kg body weight/day), which were sacrificed 7 (RG7) or 15 (RG15) days after the radiation session. Morphological and morphometric analysis of the urothelium were made. Nuclear density, lamina propria cell density and mast cells numbers per area were counted. The results showed that, in R7, epithelial thickness, epithelial cell density, and cell density in the lamina propria were not significantly affected. However, density of blood vessels in R7 was reduced by 48% (p < 0.05) and this alteration was mostly prevented by glutamine (p < 0.02). In R15, density of blood vessels in the lamina propria was not significantly modified. However, epithelial thickness was reduced by 25% (p < 0.05) in R15, and this effect was prevented by glutamine (p < 0.01). In R15, epithelial cell density was increased by 35% (p < 0.02), but glutamine did not protect against this radiation-induced increase. Cell density in the lamina propria was likewise unaffected in R15. Density of mast cells in the lamina propria was markedly reduced in R7 and R15. The density was still reduced in RG7, but a higher density in RG15 suggested a glutamine-mediated recovery. Alpha-actin positive cells in the lamina propria formed a suburothelial layer and were identified as myofibroblasts. Thickness of this layer was increased in R7, but was similar to controls in RG7, while changes in R15 and RG15 were less evident. In conclusion, pelvic radiation leads to significant acute and post-acute alterations in the composition and structural features of the vesical lamina propria and epithelium. Most of these changes, however, can be prevented by glutamine nutritional supplementation. These results emphasize, therefore, the potential use of this aminoacid as a radioprotective drug.
publishDate 2013
dc.date.available.fl_str_mv 2013-11-01
dc.date.issued.fl_str_mv 2013-04-17
dc.date.accessioned.fl_str_mv 2021-01-06T20:31:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv NEPOMUCENO, Leilane Maria Barcellos. Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica. 2013. 71 f. Tese (Doutorado em Sistema Urogenital; Sistema Cardiovascular; Técnica operatória e Cirurgia Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/12313
identifier_str_mv NEPOMUCENO, Leilane Maria Barcellos. Efeito radioprotetor da L-Glutamina na parede da bexiga de ratos submetidos à irradiação pélvica. 2013. 71 f. Tese (Doutorado em Sistema Urogenital; Sistema Cardiovascular; Técnica operatória e Cirurgia Experimental) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.
url http://www.bdtd.uerj.br/handle/1/12313
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dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro Biomédico::Faculdade de Ciências Médicas
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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