Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Carmo Filho, José Ronildo Lins do
Orientador(a): Mota, Mário Rogério Lima
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso embargado
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/74527
Resumo: Oral squamous cell carcinoma (CEC) is the most common malignant neoplasm of the oral cavity, corresponding to approximately 94% of cases in this region. Low-intensity laser demonstrates basic anti-inflammatory, analgesic and biomodulation effects, but there is no consensus in the literature regarding its role in oral malignant lesions and potentially malignant disorders, as well as in the tumor microenvironment. The objective of this work was to evaluate the influence of low-level laser therapy (LTBI) in a model of oral carcinogenesis induced by 4-nitroquinoline-n-oxide (4-NQO). For this, 96 Swiss mice were subjected to topical application of 1% 4-NQO on the surface of the lingual dorsum, daily, for 20 weeks. The animals were divided into eight groups: a negative control group (GCN) treated with 4-NQO diluent (DMSO), a positive control group (GCP) treated with 1% 4-NQO, and six experimental groups (GT) treated with with 4-NQO 1% and co-treated with LTBI [red laser (LV) and infrared laser (LIV)]: starting at week zero (GT1 with LV and GT4 with LIV), at the twelfth week (GT2 with LV and GT5 with LIV) and in the sixteenth week (GT3 with LV and GT6 with LIV). The animals were euthanized after 20 weeks and the tongues were removed for processing and making histological slides for analysis of the presence and severity of cellular and architectural alterations of the lesions (dysplastic and neoplastic), immunohistochemical reactions (Ciclin D1 and Ki-67), myeloperoxidase (MPO), n-acetyl-β-d-glucosaminidase (n-AG), malondialdehyde (MDA), reduced glutathione (GSH), total proteins, tumor necrosis factor alpha (TNF- α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). For all analyses, the statistical software GraphPad Prism 5.0® was used, with a significance level of p<0.05. The group that received only 4-NQO showed a significant increase in the frequency of carcinoma (p<0.001), an increase in the frequency (%) of positive expression for Cyclin D1 and Ki-67 (p<0.005), in addition to increased levels of TNF-α, IL-1β, IL-6, MPO, n-AG, MDA and total proteins (p<0.001) when compared to GCN; and all groups treated with laser, regardless of whether red or infrared, showed a significant reduction in these parameters. Finally, there was an increase in reduced glutathione levels only in the groups treated with LIV when compared to the 4-NQO group (p<0.001). These results show that low level laser therapy (with red and infrared laser) reduced the development of tumors in a model of oral carcinogenesis induced by 4-NQO in the tongue of mice, and this effect was accompanied by a reduction in the expression of markers associated with tumor proliferation and aggressiveness, reduced influx of inflammatory cells, cytokines associated with mechanisms of inflammation and carcinogenesis (TNF-α, IL-1β, IL-6), in addition to an improvement in tissue redox balance.
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spelling Carmo Filho, José Ronildo Lins doMota, Mário Rogério Lima2023-09-29T12:19:17Z2023-09-29T12:19:17Z2023-07-31CARMO FILHO, José Ronildo Lins do. Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos. 2023. 79 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/74527. Acesso em: 29 set. 2023.http://repositorio.ufc.br/handle/riufc/74527Oral squamous cell carcinoma (CEC) is the most common malignant neoplasm of the oral cavity, corresponding to approximately 94% of cases in this region. Low-intensity laser demonstrates basic anti-inflammatory, analgesic and biomodulation effects, but there is no consensus in the literature regarding its role in oral malignant lesions and potentially malignant disorders, as well as in the tumor microenvironment. The objective of this work was to evaluate the influence of low-level laser therapy (LTBI) in a model of oral carcinogenesis induced by 4-nitroquinoline-n-oxide (4-NQO). For this, 96 Swiss mice were subjected to topical application of 1% 4-NQO on the surface of the lingual dorsum, daily, for 20 weeks. The animals were divided into eight groups: a negative control group (GCN) treated with 4-NQO diluent (DMSO), a positive control group (GCP) treated with 1% 4-NQO, and six experimental groups (GT) treated with with 4-NQO 1% and co-treated with LTBI [red laser (LV) and infrared laser (LIV)]: starting at week zero (GT1 with LV and GT4 with LIV), at the twelfth week (GT2 with LV and GT5 with LIV) and in the sixteenth week (GT3 with LV and GT6 with LIV). The animals were euthanized after 20 weeks and the tongues were removed for processing and making histological slides for analysis of the presence and severity of cellular and architectural alterations of the lesions (dysplastic and neoplastic), immunohistochemical reactions (Ciclin D1 and Ki-67), myeloperoxidase (MPO), n-acetyl-β-d-glucosaminidase (n-AG), malondialdehyde (MDA), reduced glutathione (GSH), total proteins, tumor necrosis factor alpha (TNF- α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). For all analyses, the statistical software GraphPad Prism 5.0® was used, with a significance level of p<0.05. The group that received only 4-NQO showed a significant increase in the frequency of carcinoma (p<0.001), an increase in the frequency (%) of positive expression for Cyclin D1 and Ki-67 (p<0.005), in addition to increased levels of TNF-α, IL-1β, IL-6, MPO, n-AG, MDA and total proteins (p<0.001) when compared to GCN; and all groups treated with laser, regardless of whether red or infrared, showed a significant reduction in these parameters. Finally, there was an increase in reduced glutathione levels only in the groups treated with LIV when compared to the 4-NQO group (p<0.001). These results show that low level laser therapy (with red and infrared laser) reduced the development of tumors in a model of oral carcinogenesis induced by 4-NQO in the tongue of mice, and this effect was accompanied by a reduction in the expression of markers associated with tumor proliferation and aggressiveness, reduced influx of inflammatory cells, cytokines associated with mechanisms of inflammation and carcinogenesis (TNF-α, IL-1β, IL-6), in addition to an improvement in tissue redox balance.O carcinoma espinocelular de boca (CEC) é a neoplasia maligna mais comum da cavidade oral, correspondendo a aproximadamente 94% dos casos dessa região. O laser de baixa intensidade demonstra efeitos básicos anti-inflamatório, analgésico e de biomodulação, porém não é consenso na literatura seu papel em lesões malignas e desordens potencialmente malignas orais, bem como no microambiente tumoral. O objetivo desse trabalho foi avaliar a influência da laserterapia de baixa intensidade (LTBI) em modelo de carcinogênese oral induzida por 4-nitroquinolina-n-óxido (4-NQO). Para isso, 96 camundongos da linhagem swiss foram submetidos à aplicação tópica de 1% de 4-NQO em superfície do dorso lingual, diariamente, durante 20 semanas. Os animais foram divididos em oito grupos: um grupo controle negativo (GCN) que recebeu o diluente do 4-NQO (DMSO), um grupo controle positivo (GCP) com administração de 4-NQO 1%, e seis grupos experimentais (GT) submetidos à aplicação de 4-NQO 1% e tratados com LTBI [laser vermelho (LV) e infravermelho (LIV)]: começando na semana zero (GT1 com LV e GT4 com LIV), na décima segunda semana (GT2 com LV e GT5 com LIV) e na décima sexta semana (GT3 com LV e GT6 com LIV). Os animais foram eutanasiados ao fim das 20 semanas e as línguas foram removidas para processamento e confecção de lâminas histológicas para análise da presença e severidade das alterações celulares e arquiteturais das lesões (displásicas e neoplásicas), reações de imuno-histoquímica (Ciclina D1 e Ki-67), dosagens de mieloperoxidase (MPO), n-acetil-β-d-glicosaminidase (n-AG), malondialdeído (MDA), glutationa reduzida (GSH), proteínas totais, fator de necrose tumoral alfa (TNF-α), interleucina 1β (IL-1β) e interleucina 6 (IL-6). Para todas as análises foi utilizado o software estatístico GraphPad Prism 5.0®, com nível de significância p<0,05. O grupo que recebeu apenas 4-NQO apresentou aumento significativo da frequência de carcinoma (p<0,001), aumento da expressão nuclear positiva para Ciclina D1 e Ki-67 (p<0,005), além de aumento dos níveis de TNF-α, IL-1β, IL-6, MPO, n-AG, MDA e proteínas totais (p<0,001) quando comparados ao GCN; e todos os grupos tratados com laser, independente se vermelho ou infravermelho, apresentaram redução significativa desses parâmetros. Por fim, viu-se aumento dos níveis de glutationa reduzida apenas nos grupos tratados com LIV quando comparados ao grupo 4-NQO (p<0,001). Estes resultados evidenciam que a laserterapia de baixa potência (com laser vermelho e infravermelho) reduziu o desenvolvimento de tumores em modelo de carcinogênese oral induzido por 4-NQO na língua de camundongos, e este efeito foi acompanhado de uma redução da expressão de marcadores associados à proliferação e agressividade tumoral, redução de influxo de células inflamatórias, de citocinas associadas aos mecanismos de inflamação e carcinogênese (TNF-α, IL-1β, IL-6), além de uma melhora no equilíbrio redox tecidual.Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTerapia a LaserCarcinoma de Células Escamosas4-Nitroquinolina-1-ÓxidoCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIAinfo:eu-repo/semantics/embargoedAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0000-0002-1669-0398http://lattes.cnpq.br/1574055019631001https://orcid.org/0000-0003-3778-0584http://lattes.cnpq.br/20118329845838622025-07-30ORIGINAL2023_tese_jrlcarmofilho.pdf2023_tese_jrlcarmofilho.pdfapplication/pdf3477238http://repositorio.ufc.br/bitstream/riufc/74527/1/2023_tese_jrlcarmofilho.pdf1c2bddb8e0e0610427573db84618c248MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/74527/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/745272023-09-29 09:20:18.393oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-09-29T12:20:18Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
title Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
spellingShingle Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
Carmo Filho, José Ronildo Lins do
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
Terapia a Laser
Carcinoma de Células Escamosas
4-Nitroquinolina-1-Óxido
title_short Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
title_full Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
title_fullStr Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
title_full_unstemmed Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
title_sort Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos
author Carmo Filho, José Ronildo Lins do
author_facet Carmo Filho, José Ronildo Lins do
author_role author
dc.contributor.author.fl_str_mv Carmo Filho, José Ronildo Lins do
dc.contributor.advisor1.fl_str_mv Mota, Mário Rogério Lima
contributor_str_mv Mota, Mário Rogério Lima
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
topic CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
Terapia a Laser
Carcinoma de Células Escamosas
4-Nitroquinolina-1-Óxido
dc.subject.ptbr.pt_BR.fl_str_mv Terapia a Laser
Carcinoma de Células Escamosas
4-Nitroquinolina-1-Óxido
description Oral squamous cell carcinoma (CEC) is the most common malignant neoplasm of the oral cavity, corresponding to approximately 94% of cases in this region. Low-intensity laser demonstrates basic anti-inflammatory, analgesic and biomodulation effects, but there is no consensus in the literature regarding its role in oral malignant lesions and potentially malignant disorders, as well as in the tumor microenvironment. The objective of this work was to evaluate the influence of low-level laser therapy (LTBI) in a model of oral carcinogenesis induced by 4-nitroquinoline-n-oxide (4-NQO). For this, 96 Swiss mice were subjected to topical application of 1% 4-NQO on the surface of the lingual dorsum, daily, for 20 weeks. The animals were divided into eight groups: a negative control group (GCN) treated with 4-NQO diluent (DMSO), a positive control group (GCP) treated with 1% 4-NQO, and six experimental groups (GT) treated with with 4-NQO 1% and co-treated with LTBI [red laser (LV) and infrared laser (LIV)]: starting at week zero (GT1 with LV and GT4 with LIV), at the twelfth week (GT2 with LV and GT5 with LIV) and in the sixteenth week (GT3 with LV and GT6 with LIV). The animals were euthanized after 20 weeks and the tongues were removed for processing and making histological slides for analysis of the presence and severity of cellular and architectural alterations of the lesions (dysplastic and neoplastic), immunohistochemical reactions (Ciclin D1 and Ki-67), myeloperoxidase (MPO), n-acetyl-β-d-glucosaminidase (n-AG), malondialdehyde (MDA), reduced glutathione (GSH), total proteins, tumor necrosis factor alpha (TNF- α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). For all analyses, the statistical software GraphPad Prism 5.0® was used, with a significance level of p<0.05. The group that received only 4-NQO showed a significant increase in the frequency of carcinoma (p<0.001), an increase in the frequency (%) of positive expression for Cyclin D1 and Ki-67 (p<0.005), in addition to increased levels of TNF-α, IL-1β, IL-6, MPO, n-AG, MDA and total proteins (p<0.001) when compared to GCN; and all groups treated with laser, regardless of whether red or infrared, showed a significant reduction in these parameters. Finally, there was an increase in reduced glutathione levels only in the groups treated with LIV when compared to the 4-NQO group (p<0.001). These results show that low level laser therapy (with red and infrared laser) reduced the development of tumors in a model of oral carcinogenesis induced by 4-NQO in the tongue of mice, and this effect was accompanied by a reduction in the expression of markers associated with tumor proliferation and aggressiveness, reduced influx of inflammatory cells, cytokines associated with mechanisms of inflammation and carcinogenesis (TNF-α, IL-1β, IL-6), in addition to an improvement in tissue redox balance.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-09-29T12:19:17Z
dc.date.available.fl_str_mv 2023-09-29T12:19:17Z
dc.date.issued.fl_str_mv 2023-07-31
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 CARMO FILHO, José Ronildo Lins do. Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos. 2023. 79 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/74527. Acesso em: 29 set. 2023.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/74527
identifier_str_mv CARMO FILHO, José Ronildo Lins do. Impacto da laserterapia de baixa potência em modelo de carcinogênese oral induzido por 4-nitroquinolina-n-óxido (4-NQO) na língua de camundongos. 2023. 79 f. Tese (Doutorado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/74527. Acesso em: 29 set. 2023.
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