Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar

Detalhes bibliográficos
Autor(a) principal: Andrade, Cherley Borba Vieira de
Data de Publicação: 2010
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/16258
Resumo: Radiation therapy is one of the most commonly used therapeutic modalities in cancer treatment, aiming the destruction of neoplastic cells using ionizing radiation. A limiting factor is the radiation damage in healthy tissues neighboring the tumor. The irradiation of the skin, accidentally or for therapeutic purposes, can trigger a series of injuries culminating in fibrosis, causing functional alterations in this organ. The morphological evaluation of the effects associated with skin irradiation becomes essential to establish more effective strategies for irradiation and decreased morbidity, and in case of accidents, proper handling of the victim. The aim of this study was to evaluate the radiation-induced dermal changes, using a rats model. Male Wistar rats, three months old, had their skin irradiated, in a 3cm2 field, with single doses of 10, 40 and 60 Gy of electrons with nominal energy of 4MeV. After irradiation, the animals were kept under constant observation, lesions were recorded photographically. The animals were divided into groups and euthanized: on the day of irradiation, 5, 10, 15, 25 and 100 days after irradiation. Part of the skin was fixed in formaldehyde, embedded in paraffin and subjected to microtomy. Sections were stained with hematoxylin-eosin, picrosirius red and immunostained with anti-TGF-beta1. Another part of the tissue was fixed in glutaraldehyde and processed for scanning electron microscopy. It was observed macroscopic skin lesions similar to burns throughout the irradiated area. It was verified, by optical microscopy, the early development of lesions 5 days after irradiation. After 10 days of irradiation there was evidence of epidermal wound healing under the crust formed by the injury. At the day 15 days the tissue below the lesion was reconstructed and had characteristics of healing, displaying a significant polymorphonuclear cells infiltration. After 25 days, at the higher doses, the lesions persisted, which did not occur at the lowest dose, which the irradiated area was already completely healed. After 100 days of irradiation with 40 Gy the wound was healed. With 60 Gy, in some animals, the lesion persisted. In the animals which the healing took place there was a hypertrophy of the epidermis (acanthosis). It was observed a tissue totally morphological mischaracterized, and necrotic. The results obtained by scanning electron microscopy analysis corroborate with the optical microscopy findings, where the higher doses collagen fibers were mischaracterized. The results indicate that the doses used induced a significant inflammation in the skin, activating the immune system. This fact promoted an increased expression of TGFbeta1, which is responsible for an increased production of extracellular matrix (ECM) by various cell types, mainly fibroblasts in injured tissues. Besides the increased expression of ECM, the TGFbeta1 also promotes the inhibition of the degradation processes of the same. The intense expression of this cytokines in irradiated skin can trigger the process of fibrosis and, consequently, affect the homeostasis of the body due to accumulation of ECM.
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spelling Almeida, Carlos Eduardo Veloso dehttp://lattes.cnpq.br/6836623990976293Carvalho, Jorge José dehttp://lattes.cnpq.br/2608779267915272Corrêa, Alexandre Felip Silvahttp://lattes.cnpq.br/5628504538569473Pinheiro, Nadja Limahttp://lattes.cnpq.br/2704840396057478http://lattes.cnpq.br/4879823436707004Andrade, Cherley Borba Vieira de2021-04-26T01:15:36Z2013-11-062010-02-25ANDRADE, Cherley Borba Vieira de. Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar. 2010. 79 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010.http://www.bdtd.uerj.br/handle/1/16258Radiation therapy is one of the most commonly used therapeutic modalities in cancer treatment, aiming the destruction of neoplastic cells using ionizing radiation. A limiting factor is the radiation damage in healthy tissues neighboring the tumor. The irradiation of the skin, accidentally or for therapeutic purposes, can trigger a series of injuries culminating in fibrosis, causing functional alterations in this organ. The morphological evaluation of the effects associated with skin irradiation becomes essential to establish more effective strategies for irradiation and decreased morbidity, and in case of accidents, proper handling of the victim. The aim of this study was to evaluate the radiation-induced dermal changes, using a rats model. Male Wistar rats, three months old, had their skin irradiated, in a 3cm2 field, with single doses of 10, 40 and 60 Gy of electrons with nominal energy of 4MeV. After irradiation, the animals were kept under constant observation, lesions were recorded photographically. The animals were divided into groups and euthanized: on the day of irradiation, 5, 10, 15, 25 and 100 days after irradiation. Part of the skin was fixed in formaldehyde, embedded in paraffin and subjected to microtomy. Sections were stained with hematoxylin-eosin, picrosirius red and immunostained with anti-TGF-beta1. Another part of the tissue was fixed in glutaraldehyde and processed for scanning electron microscopy. It was observed macroscopic skin lesions similar to burns throughout the irradiated area. It was verified, by optical microscopy, the early development of lesions 5 days after irradiation. After 10 days of irradiation there was evidence of epidermal wound healing under the crust formed by the injury. At the day 15 days the tissue below the lesion was reconstructed and had characteristics of healing, displaying a significant polymorphonuclear cells infiltration. After 25 days, at the higher doses, the lesions persisted, which did not occur at the lowest dose, which the irradiated area was already completely healed. After 100 days of irradiation with 40 Gy the wound was healed. With 60 Gy, in some animals, the lesion persisted. In the animals which the healing took place there was a hypertrophy of the epidermis (acanthosis). It was observed a tissue totally morphological mischaracterized, and necrotic. The results obtained by scanning electron microscopy analysis corroborate with the optical microscopy findings, where the higher doses collagen fibers were mischaracterized. The results indicate that the doses used induced a significant inflammation in the skin, activating the immune system. This fact promoted an increased expression of TGFbeta1, which is responsible for an increased production of extracellular matrix (ECM) by various cell types, mainly fibroblasts in injured tissues. Besides the increased expression of ECM, the TGFbeta1 also promotes the inhibition of the degradation processes of the same. The intense expression of this cytokines in irradiated skin can trigger the process of fibrosis and, consequently, affect the homeostasis of the body due to accumulation of ECM.A radioterapia é uma das modalidades terapêuticas mais utilizadas no tratamento do câncer, visando à destruição das células neoplásicas, a partir da utilização de radiação ionizante. Um dos fatores limitantes da radioterapia é o dano em tecidos sadios vizinhos ao tumor. A irradiação da pele, acidental ou para fins terapêuticos, pode desencadear uma série de lesões culminando na fibrose, o que implica na alteração funcional deste órgão. A avaliação dos efeitos morfológicos associados à irradiação da pele torna-se fundamental para estabelecer estratégias de irradiação mais eficazes e diminuição da morbidade; e em caso de acidentes, adequado manuseio da vítima. O objetivo deste estudo foi avaliar as alterações dérmicas radioinduzidas, utilizando um modelo em ratos. Ratos Wistar, machos, com três meses de idade, tiveram sua pele irradiada, em um campo de 3cm2, com doses únicas de 10, 40 e 60 Gy de elétrons com energia nominal de 4MeV. Após a irradiação, os animais permaneceram sob avaliação constante, sendo as lesões registradas fotograficamente. Os animais foram divididos em grupos e eutanasiados: no dia da irradiação, 5, 10, 15, 25 e 100 dias após a irradiação. Parte da pele foi fixada em formaldeído, incluída em parafina e submetida à microtomia. Os cortes foram corados com hematoxilina-eosina, picrosirius red e imunomarcados com anticorpo anti-TGF-beta1. Outra parte do tecido foi fixada em glutaraldeido e processada para microscopia eletrônica de varredura. Foi observado macroscopicamente o surgimento de lesões cutâneas semelhantes a queimaduras em toda área irradiada. Ao microscópio óptico foi verificado o inicio de desenvolvimento de lesão 5 dias após irradiação. Decorridos 10 dias da irradiação observou-se indícios de cicatrização epidérmica abaixo da crosta formada pela lesão. Aos 15 dias após a irradiação o tecido abaixo da lesão apresentava epiderme reconstruída e características de cicatrização tecidual. Foi visualizado também um infiltrado de polimorfonucleares significativo. Após 25 dias nas doses mais elevadas as lesões persistiam, o que não ocorreu na menor dose, na qual a área irradiada dos animais já se encontrava completamente cicatrizada. Após 100 dias da irradiação na dose de 40 Gy ocorreu a cicatrização da ferida. Na dose de 60 Gy em alguns animais a lesão persistia. Nos animais em que ocorreu a cicatrização houve uma hipertrofia da epiderme (acantose). Foi visualizado um tecido com aspecto morfológico totalmente descaracterizado, e necrosado. Os resultados encontrados na analise através de microscopia eletrônica de varredura corroboram os dados encontrados na microscopia de luz, onde observou-se a descaracterização das fibras de colágeno nas doses mais elevadas. Os resultados indicam que as doses utilizadas induziram um processo inflamatório importante na pele, ativando o sistema imunológico. Este fato promoveu um aumento na expressão do TGFbeta1, um dos responsáveis pelo aumento da produção da matriz extracelular por vários tipos celulares, principalmente por fibroblastos em tecidos lesionados. Alem do aumento de expressão da MEC, o TGFbeta1 também promove a inibição dos processos de degradação da mesma. A intensa expressão desta citocina na pele irradiada pode desencadear o processo de fibrose e, conseqüentemente, afetar a homeostase deste órgão devido ao acúmulo da MEC.Submitted by Boris INFORMAT (boris@uerj.br) on 2021-04-26T01:15:36Z No. of bitstreams: 1 Cherley Borba de Andrade Dissertacao completa.pdf: 4002882 bytes, checksum: f85bbb5c63064ca7518bc54f897bbc85 (MD5)Made available in DSpace on 2021-04-26T01:15:36Z (GMT). No. of bitstreams: 1 Cherley Borba de Andrade Dissertacao completa.pdf: 4002882 bytes, checksum: f85bbb5c63064ca7518bc54f897bbc85 (MD5) Previous issue date: 2010-02-25Comissão Nacional de Energia Nuclearapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBRCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesSkinIonizing RadiationWound healingTGF-betaCollagenPeleRadiação ionizanteReparo TecidualTGF-betaColágenoPele Reparos e reconstruçãoPele Câncer ImagemRadioterapiaEfeitos de radiaçãoRadiação ionizante DosimetriaFator transformador de crescimento betaColágenoCNPQ::CIENCIAS BIOLOGICAS::BIOFISICA::RADIOLOGIA E FOTOBIOLOGIAAvaliação de alterações morfológicas da pele após lesão radioinduzida em ratos WistarEvaluation of skin morphological alterations after radio induced injury in Winstars ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALCherley Borba de Andrade Dissertacao completa.pdfapplication/pdf4002882http://www.bdtd.uerj.br/bitstream/1/16258/1/Cherley+Borba+de+Andrade+Dissertacao+completa.pdff85bbb5c63064ca7518bc54f897bbc85MD511/162582024-02-26 11:39:30.038oai:www.bdtd.uerj.br:1/16258Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:39:30Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
dc.title.alternative.eng.fl_str_mv Evaluation of skin morphological alterations after radio induced injury in Winstars rats
title Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
spellingShingle Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
Andrade, Cherley Borba Vieira de
Skin
Ionizing Radiation
Wound healing
TGF-beta
Collagen
Pele
Radiação ionizante
Reparo Tecidual
TGF-beta
Colágeno
Pele Reparos e reconstrução
Pele Câncer Imagem
Radioterapia
Efeitos de radiação
Radiação ionizante Dosimetria
Fator transformador de crescimento beta
Colágeno
CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA::RADIOLOGIA E FOTOBIOLOGIA
title_short Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
title_full Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
title_fullStr Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
title_full_unstemmed Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
title_sort Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar
author Andrade, Cherley Borba Vieira de
author_facet Andrade, Cherley Borba Vieira de
author_role author
dc.contributor.advisor1.fl_str_mv Almeida, Carlos Eduardo Veloso de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6836623990976293
dc.contributor.referee1.fl_str_mv Carvalho, Jorge José de
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/2608779267915272
dc.contributor.referee2.fl_str_mv Corrêa, Alexandre Felip Silva
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/5628504538569473
dc.contributor.referee3.fl_str_mv Pinheiro, Nadja Lima
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/2704840396057478
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4879823436707004
dc.contributor.author.fl_str_mv Andrade, Cherley Borba Vieira de
contributor_str_mv Almeida, Carlos Eduardo Veloso de
Carvalho, Jorge José de
Corrêa, Alexandre Felip Silva
Pinheiro, Nadja Lima
dc.subject.eng.fl_str_mv Skin
Ionizing Radiation
Wound healing
TGF-beta
Collagen
topic Skin
Ionizing Radiation
Wound healing
TGF-beta
Collagen
Pele
Radiação ionizante
Reparo Tecidual
TGF-beta
Colágeno
Pele Reparos e reconstrução
Pele Câncer Imagem
Radioterapia
Efeitos de radiação
Radiação ionizante Dosimetria
Fator transformador de crescimento beta
Colágeno
CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA::RADIOLOGIA E FOTOBIOLOGIA
dc.subject.por.fl_str_mv Pele
Radiação ionizante
Reparo Tecidual
TGF-beta
Colágeno
Pele Reparos e reconstrução
Pele Câncer Imagem
Radioterapia
Efeitos de radiação
Radiação ionizante Dosimetria
Fator transformador de crescimento beta
Colágeno
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOFISICA::RADIOLOGIA E FOTOBIOLOGIA
description Radiation therapy is one of the most commonly used therapeutic modalities in cancer treatment, aiming the destruction of neoplastic cells using ionizing radiation. A limiting factor is the radiation damage in healthy tissues neighboring the tumor. The irradiation of the skin, accidentally or for therapeutic purposes, can trigger a series of injuries culminating in fibrosis, causing functional alterations in this organ. The morphological evaluation of the effects associated with skin irradiation becomes essential to establish more effective strategies for irradiation and decreased morbidity, and in case of accidents, proper handling of the victim. The aim of this study was to evaluate the radiation-induced dermal changes, using a rats model. Male Wistar rats, three months old, had their skin irradiated, in a 3cm2 field, with single doses of 10, 40 and 60 Gy of electrons with nominal energy of 4MeV. After irradiation, the animals were kept under constant observation, lesions were recorded photographically. The animals were divided into groups and euthanized: on the day of irradiation, 5, 10, 15, 25 and 100 days after irradiation. Part of the skin was fixed in formaldehyde, embedded in paraffin and subjected to microtomy. Sections were stained with hematoxylin-eosin, picrosirius red and immunostained with anti-TGF-beta1. Another part of the tissue was fixed in glutaraldehyde and processed for scanning electron microscopy. It was observed macroscopic skin lesions similar to burns throughout the irradiated area. It was verified, by optical microscopy, the early development of lesions 5 days after irradiation. After 10 days of irradiation there was evidence of epidermal wound healing under the crust formed by the injury. At the day 15 days the tissue below the lesion was reconstructed and had characteristics of healing, displaying a significant polymorphonuclear cells infiltration. After 25 days, at the higher doses, the lesions persisted, which did not occur at the lowest dose, which the irradiated area was already completely healed. After 100 days of irradiation with 40 Gy the wound was healed. With 60 Gy, in some animals, the lesion persisted. In the animals which the healing took place there was a hypertrophy of the epidermis (acanthosis). It was observed a tissue totally morphological mischaracterized, and necrotic. The results obtained by scanning electron microscopy analysis corroborate with the optical microscopy findings, where the higher doses collagen fibers were mischaracterized. The results indicate that the doses used induced a significant inflammation in the skin, activating the immune system. This fact promoted an increased expression of TGFbeta1, which is responsible for an increased production of extracellular matrix (ECM) by various cell types, mainly fibroblasts in injured tissues. Besides the increased expression of ECM, the TGFbeta1 also promotes the inhibition of the degradation processes of the same. The intense expression of this cytokines in irradiated skin can trigger the process of fibrosis and, consequently, affect the homeostasis of the body due to accumulation of ECM.
publishDate 2010
dc.date.issued.fl_str_mv 2010-02-25
dc.date.available.fl_str_mv 2013-11-06
dc.date.accessioned.fl_str_mv 2021-04-26T01:15:36Z
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 ANDRADE, Cherley Borba Vieira de. Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar. 2010. 79 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/16258
identifier_str_mv ANDRADE, Cherley Borba Vieira de. Avaliação de alterações morfológicas da pele após lesão radioinduzida em ratos Wistar. 2010. 79 f. Dissertação (Mestrado em Biociências Nucleares; Ecologia) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2010.
url http://www.bdtd.uerj.br/handle/1/16258
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dc.publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Biociências
dc.publisher.initials.fl_str_mv UERJ
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
publisher.none.fl_str_mv Universidade do Estado do Rio de Janeiro
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