Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?

Detalhes bibliográficos
Autor(a) principal: LIMA, Rafael de Abreu
Data de Publicação: 2023
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/4959
Resumo: Endometriosis is a chronic and debilitating disease associated with pelvic pain and infertility affecting women in the reproductive phase. In addition to the diagnosis being delayed in most cases, clinical treatments are not as effective, as they do not definitively treat. The pathogenesis of endometriosis is similar to that of tumors, the process of angiogenesis is quite evident, mainly with the presence of proteins that stimulate the proliferation of endothelial cells, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FCFβ). New treatment strategies have been researched, however, contested. In this context, thalidomide reappears as a pharmacological treatment modality and it can be hypothesized that in adjusted doses, it can produce a therapeutic effect. The objective of this work was to evaluate the antivasogenic and healing effects of thalidomide in the experimental model of endometriosis in rats. Thirty-six female Wistar rats were used, which were submitted to the experimental protocol of endometrial autotransplantation. After diagnosis of endometriosis, the animals were divided into 6 groups: Group A: sham, Group B: negative control, Groups treated with thalidomide at different doses (C: 25mg/kg, D: 50mg/kg and E: 100mg/kg) and Group F: treated with leuprolide (1mg/kg). After 21 days of treatment, the animals were euthanized and the liver, kidney and uterine horns were collected for immunohistochemical (Anti-VEGF) and histological (fibroblasts and toxicity) evaluation. The results demonstrate that the rats treated with thalidomide in groups D (pvalue 0.014) and E (pvalue 0.017) and leuprolide (pvalue 0.001) had the volumes of the endometriotic implants inhibited, when compared to the other groups. Histologically, there were decreases in VEGF and FCFβ expression in groups D, E and F. It was also evidenced, morphological alterations in the hepatic parenchyma of the groups D, E and F. It is concluted, for the model proposed in this research, that thalidomide provides volumetric and histopathological recovery in implants, especially in groups treated with doses of 50 and 100 mg/kg, producing a satisfactory antivasogenic and healing effect, however, there are indications of lesions in the hepatic parenchyma of these groups. It is suggested that thalidomide may be effective in the treatment of endometriosis.
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spelling GARCIA, João Batista Santoshttp://lattes.cnpq.br/0424234103760462CARVALHO, Rafael Cardosohttp://lattes.cnpq.br/3863794712744490GARCIA, João Batista Santoshttp://lattes.cnpq.br/0424234103760462CARTÁGENES, Maria do Socorro Sousahttp://lattes.cnpq.br/3013333572719007SOUSA, Joicy Cortez de Sáhttp://lattes.cnpq.br/2368453114845145SOUSA, Eduardo Martins dehttp://lattes.cnpq.br/4448263553675550OLIVEIRA, Renata Mondego dehttp://lattes.cnpq.br/8389094419884160http://lattes.cnpq.br/7556146608199418LIMA, Rafael de Abreu2023-09-20T13:51:58Z2023-09-01LIMA, Rafael de Abreu. Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?. 2023. 72 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.https://tedebc.ufma.br/jspui/handle/tede/tede/4959Endometriosis is a chronic and debilitating disease associated with pelvic pain and infertility affecting women in the reproductive phase. In addition to the diagnosis being delayed in most cases, clinical treatments are not as effective, as they do not definitively treat. The pathogenesis of endometriosis is similar to that of tumors, the process of angiogenesis is quite evident, mainly with the presence of proteins that stimulate the proliferation of endothelial cells, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FCFβ). New treatment strategies have been researched, however, contested. In this context, thalidomide reappears as a pharmacological treatment modality and it can be hypothesized that in adjusted doses, it can produce a therapeutic effect. The objective of this work was to evaluate the antivasogenic and healing effects of thalidomide in the experimental model of endometriosis in rats. Thirty-six female Wistar rats were used, which were submitted to the experimental protocol of endometrial autotransplantation. After diagnosis of endometriosis, the animals were divided into 6 groups: Group A: sham, Group B: negative control, Groups treated with thalidomide at different doses (C: 25mg/kg, D: 50mg/kg and E: 100mg/kg) and Group F: treated with leuprolide (1mg/kg). After 21 days of treatment, the animals were euthanized and the liver, kidney and uterine horns were collected for immunohistochemical (Anti-VEGF) and histological (fibroblasts and toxicity) evaluation. The results demonstrate that the rats treated with thalidomide in groups D (pvalue 0.014) and E (pvalue 0.017) and leuprolide (pvalue 0.001) had the volumes of the endometriotic implants inhibited, when compared to the other groups. Histologically, there were decreases in VEGF and FCFβ expression in groups D, E and F. It was also evidenced, morphological alterations in the hepatic parenchyma of the groups D, E and F. It is concluted, for the model proposed in this research, that thalidomide provides volumetric and histopathological recovery in implants, especially in groups treated with doses of 50 and 100 mg/kg, producing a satisfactory antivasogenic and healing effect, however, there are indications of lesions in the hepatic parenchyma of these groups. It is suggested that thalidomide may be effective in the treatment of endometriosis.A endometriose é uma doença crônica e debilitante associada a dor pélvica e infertilidade acometendo mulheres em fase reprodutiva. Além do diagnóstico ser tardio na maioria das vezes, os tratamentos clínicos não são tão eficazes, pois não tratam definitivamente. A patogênese da endometriose é semelhante à de tumores, o processo de angiogênese é bem evidente, principalmente com a presença de proteínas que estimulam a proliferação de células endoteriais como, o fator de crescimento endotelial vascular (VEGF) e o fator de crescimento de fibroblastos (FCFβ). Novas estratégias de tratamento têm sido pesquisadas, porém, contestadas. Neste contexto, a talidomida, ressurge como modalidade de tratamento farmacológico e pode- se hipotetizar que em doses ajustadas, possa produzir um efeito terapêutico. O objetivo desse trabalho foi avaliar os efeitos antivasogênico e cicatrizantes da talidomida no modelo experimental de endometriose em ratas. Foram utilizadas 36 ratas da linhagem Wistar, as quais foram submetidas ao protocolo experimental de autotransplante de endométrio. Após diagnóstico da endometriose os animais foram divididos em 6 grupos: Grupo A: sham, Grupo B: controle negativo, Grupos tratados com talidomida em diferentes doses (C: 25mg/kg, D: 50mg/kg e E: 100mg/kg) e Grupo F: tratado com leuprolida (1mg/kg). Após 21 dias de tratamento os animais foram eutanasiados e o fígado, rim e os cornos uterinos foram coletados, para avaliação imunohistoquímica (Anti-VEGF) e histológica (fibroblastos e toxicidade). Os resultados demonstram que as ratas tratadas com talidomida dos grupos D (pvalor 0,014) e E (pvalor 0,017) e leuprolida (pvalor 0,001) tiveram os volumes dos implantes endometrióticos inibidos, quando comparados aos demais grupos. Histologicamente houve diminuições na expressão do VEGF e FCFβ nos grupos D, E e F. Ficou evidenciado ainda, alterações morfológicas no parênquima hepático do grupo D, E e F. Conclui-se que, para o modelo proposto nesta pesquisa, a talidomida proporciona uma recuperação volumétrica e histopatológica em implantes, principalmente nos grupos tratados com doses de 50 e 100 mg/kg produzindo efeito antivasogênico e cicatrizante satisfatório, contudo, há indícios de lesões no parênquima hepático destes grupos. Sugere-se então, que a talidomida possa ser eficaz no tratamento da endometriose.Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2023-09-20T13:51:58Z No. of bitstreams: 1 RAFAELDEABREULIMA.pdf: 3052359 bytes, checksum: 2e34843edd73a4d6373c6578bd71d7f4 (MD5)Made available in DSpace on 2023-09-20T13:51:58Z (GMT). No. of bitstreams: 1 RAFAELDEABREULIMA.pdf: 3052359 bytes, checksum: 2e34843edd73a4d6373c6578bd71d7f4 (MD5) Previous issue date: 2023-09-01FAPEMAapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBSUFMABrasilDEPARTAMENTO DE MEDICINA II/CCBSendometriose;tratamento;talidomida;Fator de Crescimento Endotelial Vasogênico (VEGF);ratas.endometriosis;treatment;thalidomide;Vasogenic Endothelial Growth Factor (VEGF);rats.Ciências da SaúdeTratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?Treatment of experimental endometriosis: does thalidomide produce a satisfactory antivasogenic effect?info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALRAFAELDEABREULIMA.pdfRAFAELDEABREULIMA.pdfapplication/pdf3052359http://tedebc.ufma.br:8080/bitstream/tede/4959/2/RAFAELDEABREULIMA.pdf2e34843edd73a4d6373c6578bd71d7f4MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/4959/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/49592023-09-20 10:51:58.578oai:tede2: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Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312023-09-20T13:51:58Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false
dc.title.por.fl_str_mv Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
dc.title.alternative.eng.fl_str_mv Treatment of experimental endometriosis: does thalidomide produce a satisfactory antivasogenic effect?
title Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
spellingShingle Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
LIMA, Rafael de Abreu
endometriose;
tratamento;
talidomida;
Fator de Crescimento Endotelial Vasogênico (VEGF);
ratas.
endometriosis;
treatment;
thalidomide;
Vasogenic Endothelial Growth Factor (VEGF);
rats.
Ciências da Saúde
title_short Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
title_full Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
title_fullStr Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
title_full_unstemmed Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
title_sort Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?
author LIMA, Rafael de Abreu
author_facet LIMA, Rafael de Abreu
author_role author
dc.contributor.advisor1.fl_str_mv GARCIA, João Batista Santos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0424234103760462
dc.contributor.advisor-co1.fl_str_mv CARVALHO, Rafael Cardoso
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/3863794712744490
dc.contributor.referee1.fl_str_mv GARCIA, João Batista Santos
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0424234103760462
dc.contributor.referee2.fl_str_mv CARTÁGENES, Maria do Socorro Sousa
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/3013333572719007
dc.contributor.referee3.fl_str_mv SOUSA, Joicy Cortez de Sá
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/2368453114845145
dc.contributor.referee4.fl_str_mv SOUSA, Eduardo Martins de
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/4448263553675550
dc.contributor.referee5.fl_str_mv OLIVEIRA, Renata Mondego de
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/8389094419884160
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7556146608199418
dc.contributor.author.fl_str_mv LIMA, Rafael de Abreu
contributor_str_mv GARCIA, João Batista Santos
CARVALHO, Rafael Cardoso
GARCIA, João Batista Santos
CARTÁGENES, Maria do Socorro Sousa
SOUSA, Joicy Cortez de Sá
SOUSA, Eduardo Martins de
OLIVEIRA, Renata Mondego de
dc.subject.por.fl_str_mv endometriose;
tratamento;
talidomida;
Fator de Crescimento Endotelial Vasogênico (VEGF);
ratas.
topic endometriose;
tratamento;
talidomida;
Fator de Crescimento Endotelial Vasogênico (VEGF);
ratas.
endometriosis;
treatment;
thalidomide;
Vasogenic Endothelial Growth Factor (VEGF);
rats.
Ciências da Saúde
dc.subject.eng.fl_str_mv endometriosis;
treatment;
thalidomide;
Vasogenic Endothelial Growth Factor (VEGF);
rats.
dc.subject.cnpq.fl_str_mv Ciências da Saúde
description Endometriosis is a chronic and debilitating disease associated with pelvic pain and infertility affecting women in the reproductive phase. In addition to the diagnosis being delayed in most cases, clinical treatments are not as effective, as they do not definitively treat. The pathogenesis of endometriosis is similar to that of tumors, the process of angiogenesis is quite evident, mainly with the presence of proteins that stimulate the proliferation of endothelial cells, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FCFβ). New treatment strategies have been researched, however, contested. In this context, thalidomide reappears as a pharmacological treatment modality and it can be hypothesized that in adjusted doses, it can produce a therapeutic effect. The objective of this work was to evaluate the antivasogenic and healing effects of thalidomide in the experimental model of endometriosis in rats. Thirty-six female Wistar rats were used, which were submitted to the experimental protocol of endometrial autotransplantation. After diagnosis of endometriosis, the animals were divided into 6 groups: Group A: sham, Group B: negative control, Groups treated with thalidomide at different doses (C: 25mg/kg, D: 50mg/kg and E: 100mg/kg) and Group F: treated with leuprolide (1mg/kg). After 21 days of treatment, the animals were euthanized and the liver, kidney and uterine horns were collected for immunohistochemical (Anti-VEGF) and histological (fibroblasts and toxicity) evaluation. The results demonstrate that the rats treated with thalidomide in groups D (pvalue 0.014) and E (pvalue 0.017) and leuprolide (pvalue 0.001) had the volumes of the endometriotic implants inhibited, when compared to the other groups. Histologically, there were decreases in VEGF and FCFβ expression in groups D, E and F. It was also evidenced, morphological alterations in the hepatic parenchyma of the groups D, E and F. It is concluted, for the model proposed in this research, that thalidomide provides volumetric and histopathological recovery in implants, especially in groups treated with doses of 50 and 100 mg/kg, producing a satisfactory antivasogenic and healing effect, however, there are indications of lesions in the hepatic parenchyma of these groups. It is suggested that thalidomide may be effective in the treatment of endometriosis.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-09-20T13:51:58Z
dc.date.issued.fl_str_mv 2023-09-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv LIMA, Rafael de Abreu. Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?. 2023. 72 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/4959
identifier_str_mv LIMA, Rafael de Abreu. Tratamento da endometriose experimental: a talidomida produz efeito antivasogênico satisfatório?. 2023. 72 f. Tese (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.
url https://tedebc.ufma.br/jspui/handle/tede/tede/4959
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Universidade Federal do Maranhão
dc.publisher.program.fl_str_mv PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS
dc.publisher.initials.fl_str_mv UFMA
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv DEPARTAMENTO DE MEDICINA II/CCBS
publisher.none.fl_str_mv Universidade Federal do Maranhão
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