Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: Freitas, Amanda de Oliveira
Orientador(a): Alves, Ana Paula Negreiros Nunes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/77717
Resumo: Resveratrol (RSV) is a natural product that has potential in cancer chemoprevention through several molecular targets. The aim of this work was to evaluate the role of RSV in tumor initiation and progression in animal model of oral carcinogenesis induced by 1% 4-nitroquinoline 1-oxide (4NQO). In this sense, 60 Swiss mice were subjected to application of 1% 4NQO on the surface of the tongue five times a week for 20 weeks. The animals were divided into six groups: negative control group (GCN); RSV control group (GCRSV); positive control group (GCP) with 4NQO; and three experimental groups: 4NQO with RSV for 6 weeks (RSV6), 4NQO with RSV for 10 weeks (RSV10) and 4NQO with RSV for 20 weeks (RSV20). RSV was administered at a dose of 8mg/kg/day by gavage. Then, the animals were euthanized after 20 weeks and the tongues were collected for histological analysis. Blood and organ collection was performed for toxicity analysis. For all results, the p<0.05 significance level was considered. Exposure to 4NQO promoted macroscopic changes in the tongue, such as elevations and plaques, and microscopic changes, with the development of microinvasive carcinoma to extensive tissue invasion (p<0.001). Hematological analysis revealed significant leukocytosis in all groups in contact with 4NQO (p<0.001). Regarding systemic toxicity, non-exposure to 4NQO resulted in a significant body mass gain (p<0.001). Microscopic changes were observed in the esophagus, intestine, and liver. When comparing groups, a significant change in the mass of the liver, kidney and spleen was also detected. In conclusion, the present model is capable of developing epithelial changes in the tongue, from severe dysplasias to carcinomas with extensive invasion of adjacent tissues, as well as the esophageal, splenic, hepatic, renal and intestinal levels, potentiating hematological dysregulation and reducing body mass. However, the use of RSV does not interfere with tumor initiation and progression, despite having a protective effect on intestinal villi when used for at least 10 weeks and attenuating the inflammatory infiltrate and the degree of keratinization in the tongue tumor regions when used for 20 weeks.
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spelling Freitas, Amanda de OliveiraSilva, Paulo Goberlânio de BarrosAlves, Ana Paula Negreiros Nunes2024-08-19T18:31:23Z2024-08-19T18:31:23Z2024FREITAS, Amanda de Oliveira. Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos. 2024. 64 f. Dissertação (Mestrado Acadêmico em Medicina Translacional) - Faculdade de Medicina, Programa de Pós-Graduação em Medicina Translacional, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77717. Acesso em: 19 ago. 2024.http://repositorio.ufc.br/handle/riufc/77717Resveratrol (RSV) is a natural product that has potential in cancer chemoprevention through several molecular targets. The aim of this work was to evaluate the role of RSV in tumor initiation and progression in animal model of oral carcinogenesis induced by 1% 4-nitroquinoline 1-oxide (4NQO). In this sense, 60 Swiss mice were subjected to application of 1% 4NQO on the surface of the tongue five times a week for 20 weeks. The animals were divided into six groups: negative control group (GCN); RSV control group (GCRSV); positive control group (GCP) with 4NQO; and three experimental groups: 4NQO with RSV for 6 weeks (RSV6), 4NQO with RSV for 10 weeks (RSV10) and 4NQO with RSV for 20 weeks (RSV20). RSV was administered at a dose of 8mg/kg/day by gavage. Then, the animals were euthanized after 20 weeks and the tongues were collected for histological analysis. Blood and organ collection was performed for toxicity analysis. For all results, the p<0.05 significance level was considered. Exposure to 4NQO promoted macroscopic changes in the tongue, such as elevations and plaques, and microscopic changes, with the development of microinvasive carcinoma to extensive tissue invasion (p<0.001). Hematological analysis revealed significant leukocytosis in all groups in contact with 4NQO (p<0.001). Regarding systemic toxicity, non-exposure to 4NQO resulted in a significant body mass gain (p<0.001). Microscopic changes were observed in the esophagus, intestine, and liver. When comparing groups, a significant change in the mass of the liver, kidney and spleen was also detected. In conclusion, the present model is capable of developing epithelial changes in the tongue, from severe dysplasias to carcinomas with extensive invasion of adjacent tissues, as well as the esophageal, splenic, hepatic, renal and intestinal levels, potentiating hematological dysregulation and reducing body mass. However, the use of RSV does not interfere with tumor initiation and progression, despite having a protective effect on intestinal villi when used for at least 10 weeks and attenuating the inflammatory infiltrate and the degree of keratinization in the tongue tumor regions when used for 20 weeks.O Resveratrol (RSV) é um produto natural que apresenta potencial na quimioprevenção do câncer através de diversos alvos moleculares. O objetivo deste trabalho foi avaliar o efeito do RSV na iniciação e progressão tumoral em modelo animal de carcinogênese oral induzida por 4-nitroquinolina 1-óxido (4NQO). Para isso, 60 camundongos Swiss foram submetidos à aplicação de 4NQO1% sobre a superfície de língua, cinco vezes na semana, por 20 semanas. Os animais foram divididos em seis grupos: grupo controle negativo (GCN); grupo controle RSV (GCRSV); grupo controle positivo (GCP) com 4NQO; e três grupos experimentais: 4NQO com RSV por 6 semanas (RSV6), 4NQO com RSV por 10 semanas (RSV10) e 4NQO com RSV por 20 semanas (RSV20). O RSV foi administrado na dose de 8mg/kg/dia por gavagem. Os animais foram eutanasiados após 20 semanas para excisão das línguas e posterior análise histológica. Coleta de sangue e de órgãos foi realizada para análise de toxicidade. Para todos os resultados foi considerado o nível de significância p<0,05. A exposição ao 4NQO promoveu alterações macroscópicas em língua, como elevações e placas,e microscópicas, com o desenvolvimento desde carcinoma microinvasor até invasão extensiva dos tecidos (p<0,001). A análise hematológica revelou leucocitose significativa em todos os grupos em contato com o 4NQO (p<0,001). No que tange à toxicidade sistêmica, a não exposição ao 4NQO implicou em ganho significativo de massa corpórea (p<0,001). Observou-se alterações microscópicas em esôfago, intestino e fígado. Na comparação entre grupos, foi observada alteração significativa na massa do fígado, rim e baço. Conclui-se que o presente modelo é capaz de desenvolver alterações epiteliais em língua, desde displasias severas até carcinomas com invasão extensiva de tecidos adjacentes, bem como em nível esofágico, esplênico, hepático, renal, intestinal e potencializar a desregulação hematológica, bem como reduzir massa corpórea. Porém, a utilização do RSV não interferiu na iniciação e progressão tumoral, apesar de apresentar efeito protetor dos vilos intestinais quando utilizado por pelo menos 10 semanas e atenuar o infiltrado inflamatório e o grau de queratinização nas regiões dos tumores de língua quando utilizado por 20 semanas.Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisResveratrolapoptoseCarcinogêneseCarcinoma de Células EscamosasResveratrolApoptosisCarcinogenesisCarcinoma, Squamous CellCNPQ::CIENCIAS DA SAUDE::MEDICINAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/3015264819157635http://lattes.cnpq.br/5522921433940881https://orcid.org/0000-0002-1513-9027http://lattes.cnpq.br/43077207498308192024LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/77717/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53ORIGINAL2024_dis_adofreitas.pdf2024_dis_adofreitas.pdfapplication/pdf2841364http://repositorio.ufc.br/bitstream/riufc/77717/4/2024_dis_adofreitas.pdf7ab45572b99818c192da6ccf6636990aMD54riufc/777172024-11-14 13:15:48.413oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-11-14T16:15:48Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
title Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
spellingShingle Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
Freitas, Amanda de Oliveira
CNPQ::CIENCIAS DA SAUDE::MEDICINA
Resveratrol
apoptose
Carcinogênese
Carcinoma de Células Escamosas
Resveratrol
Apoptosis
Carcinogenesis
Carcinoma, Squamous Cell
title_short Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
title_full Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
title_fullStr Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
title_full_unstemmed Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
title_sort Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos
author Freitas, Amanda de Oliveira
author_facet Freitas, Amanda de Oliveira
author_role author
dc.contributor.co-advisor.none.fl_str_mv Silva, Paulo Goberlânio de Barros
dc.contributor.author.fl_str_mv Freitas, Amanda de Oliveira
dc.contributor.advisor1.fl_str_mv Alves, Ana Paula Negreiros Nunes
contributor_str_mv Alves, Ana Paula Negreiros Nunes
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA
Resveratrol
apoptose
Carcinogênese
Carcinoma de Células Escamosas
Resveratrol
Apoptosis
Carcinogenesis
Carcinoma, Squamous Cell
dc.subject.ptbr.pt_BR.fl_str_mv Resveratrol
apoptose
Carcinogênese
Carcinoma de Células Escamosas
dc.subject.en.pt_BR.fl_str_mv Resveratrol
Apoptosis
Carcinogenesis
Carcinoma, Squamous Cell
description Resveratrol (RSV) is a natural product that has potential in cancer chemoprevention through several molecular targets. The aim of this work was to evaluate the role of RSV in tumor initiation and progression in animal model of oral carcinogenesis induced by 1% 4-nitroquinoline 1-oxide (4NQO). In this sense, 60 Swiss mice were subjected to application of 1% 4NQO on the surface of the tongue five times a week for 20 weeks. The animals were divided into six groups: negative control group (GCN); RSV control group (GCRSV); positive control group (GCP) with 4NQO; and three experimental groups: 4NQO with RSV for 6 weeks (RSV6), 4NQO with RSV for 10 weeks (RSV10) and 4NQO with RSV for 20 weeks (RSV20). RSV was administered at a dose of 8mg/kg/day by gavage. Then, the animals were euthanized after 20 weeks and the tongues were collected for histological analysis. Blood and organ collection was performed for toxicity analysis. For all results, the p<0.05 significance level was considered. Exposure to 4NQO promoted macroscopic changes in the tongue, such as elevations and plaques, and microscopic changes, with the development of microinvasive carcinoma to extensive tissue invasion (p<0.001). Hematological analysis revealed significant leukocytosis in all groups in contact with 4NQO (p<0.001). Regarding systemic toxicity, non-exposure to 4NQO resulted in a significant body mass gain (p<0.001). Microscopic changes were observed in the esophagus, intestine, and liver. When comparing groups, a significant change in the mass of the liver, kidney and spleen was also detected. In conclusion, the present model is capable of developing epithelial changes in the tongue, from severe dysplasias to carcinomas with extensive invasion of adjacent tissues, as well as the esophageal, splenic, hepatic, renal and intestinal levels, potentiating hematological dysregulation and reducing body mass. However, the use of RSV does not interfere with tumor initiation and progression, despite having a protective effect on intestinal villi when used for at least 10 weeks and attenuating the inflammatory infiltrate and the degree of keratinization in the tongue tumor regions when used for 20 weeks.
publishDate 2024
dc.date.accessioned.fl_str_mv 2024-08-19T18:31:23Z
dc.date.available.fl_str_mv 2024-08-19T18:31:23Z
dc.date.issued.fl_str_mv 2024
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv FREITAS, Amanda de Oliveira. Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos. 2024. 64 f. Dissertação (Mestrado Acadêmico em Medicina Translacional) - Faculdade de Medicina, Programa de Pós-Graduação em Medicina Translacional, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77717. Acesso em: 19 ago. 2024.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/77717
identifier_str_mv FREITAS, Amanda de Oliveira. Avaliação do efeito do Resveratrol na carcinogênese oral induzida por 4-nitroquinolina 1-óxido em camundongos. 2024. 64 f. Dissertação (Mestrado Acadêmico em Medicina Translacional) - Faculdade de Medicina, Programa de Pós-Graduação em Medicina Translacional, Universidade Federal do Ceará, Fortaleza, 2024. Disponível em: http://www.repositorio.ufc.br/handle/riufc/ 77717. Acesso em: 19 ago. 2024.
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