Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)

Oral mucositis (OM) is a debilitating side effect often present in patients undergoing cancer treatment, which affects the oral cavity or oropharynx. Lesions resulting from OM can compromise the quality of life of patients undergoing radiotherapy and / or chemotherapy, as well as contribute to the s...

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Autor principal: Barbosa, Maisie Mitchele
Outros Autores: Medeiros, Caroline Addison Carvalho Xavier de
Formato: Dissertação
Idioma:por
Publicado em: Brasil
Assuntos:
Mucosite oral
Inflamação
5-Fluorouracil
Telmisartana
CNPQ::CIENCIAS BIOLOGICAS
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/25147
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id ri-123456789-25147
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language por
topic Mucosite oral
Inflamação
5-Fluorouracil
Telmisartana
CNPQ::CIENCIAS BIOLOGICAS
spellingShingle Mucosite oral
Inflamação
5-Fluorouracil
Telmisartana
CNPQ::CIENCIAS BIOLOGICAS
Barbosa, Maisie Mitchele
Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
description Oral mucositis (OM) is a debilitating side effect often present in patients undergoing cancer treatment, which affects the oral cavity or oropharynx. Lesions resulting from OM can compromise the quality of life of patients undergoing radiotherapy and / or chemotherapy, as well as contribute to the suspension of the cancer treatment protocol. This study aims to evaluate the anti-inflammatory effects of Telmisartan (TELM), an angiotensin II receptor antagonist, in an experimental model of oral mucositis induced by the 5-fluorouracil (5-FU) chemotherapy in hamsters. In the course of 10 days, groups of animals submitted to 5-FU were treated with telmisartan at doses of 1, 5 or 10 mg/Kg. The animals received intraperitoneal injection of 5-fluorouracil on 1th and 2th day, at doses of 60 and 40 mg/Kg, respectively, and had their right jugal pouch everted and scratched superficially on the 4th day. The animals were euthanized on day 10 and blood and mucosa samples were collected. The mucosa was evaluated clinically, through the assignment of scores after macroscopic and histopathological analysis. TNF-α and IL-1β levels were determined by the ELISA. Immunohistochemical analyzes for MMP-9, COX-2 and TGF-β, immunofluorescence for iNOS and NF-κB/p65, protein expression for SMAD 2/3 by Western blot and RT-PCR for STAT1, PPAR-γ and NF-κB/p65 were performed. Blood samples were used to evaluate hepatic and renal function as well as for leukocyte count. The results showed that Telmisartan at doses of 5 or 10 mg/Kg prevented the inflammatory effects of OM, with a decrease in macroscopic and histopathological (p < 0,05) and proinflammatory cytokine levels TNF-α and IL-1β (p < 0,05). TELM at the dose of 10 mg/Kg decreased the immunostaining for MMP-9, COX-2 and TGF-β, reduced immunoexpression for iNOS and NF-κB/p65 and protein expression of SMAD 2/3. TELM at doses of 5 or 10 mg/Kg reduced the gene expression of STAT1 and NF-κB/p65 and increased PPAR-γ expression, compared to the 5-FU group. The groups treated with TELM at doses of 1, 5 or 10 mg/Kg did not show significant difference (p < 0,05) in liver and renal function levels and showed a decrease in the number of leukocytes when compared to the 5-FU group. Thus, the drug Telmisartan had a protective effect on MO induced in hamsters, however, further studies are still needed.
author2 Medeiros, Caroline Addison Carvalho Xavier de
author_facet Medeiros, Caroline Addison Carvalho Xavier de
Barbosa, Maisie Mitchele
format masterThesis
author Barbosa, Maisie Mitchele
author_sort Barbosa, Maisie Mitchele
title Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
title_short Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
title_full Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
title_fullStr Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
title_full_unstemmed Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus)
title_sort efeito da telmisartana no modelo de mucosite oral induzida por 5-fluorouracil em hamsters golden syriam (mesocricetus auratus)
publisher Brasil
publishDate 2018
url https://repositorio.ufrn.br/jspui/handle/123456789/25147
work_keys_str_mv AT barbosamaisiemitchele efeitodatelmisartananomodelodemucositeoralinduzidapor5fluorouracilemhamstersgoldensyriammesocricetusauratus
_version_ 1773966474452402176
spelling ri-123456789-251472019-02-07T04:47:50Z Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus) Barbosa, Maisie Mitchele Medeiros, Caroline Addison Carvalho Xavier de Araújo, Aurigena Antunes de Barbosa, Patricia Batista Barra Medeiros Mucosite oral Inflamação 5-Fluorouracil Telmisartana CNPQ::CIENCIAS BIOLOGICAS Oral mucositis (OM) is a debilitating side effect often present in patients undergoing cancer treatment, which affects the oral cavity or oropharynx. Lesions resulting from OM can compromise the quality of life of patients undergoing radiotherapy and / or chemotherapy, as well as contribute to the suspension of the cancer treatment protocol. This study aims to evaluate the anti-inflammatory effects of Telmisartan (TELM), an angiotensin II receptor antagonist, in an experimental model of oral mucositis induced by the 5-fluorouracil (5-FU) chemotherapy in hamsters. In the course of 10 days, groups of animals submitted to 5-FU were treated with telmisartan at doses of 1, 5 or 10 mg/Kg. The animals received intraperitoneal injection of 5-fluorouracil on 1th and 2th day, at doses of 60 and 40 mg/Kg, respectively, and had their right jugal pouch everted and scratched superficially on the 4th day. The animals were euthanized on day 10 and blood and mucosa samples were collected. The mucosa was evaluated clinically, through the assignment of scores after macroscopic and histopathological analysis. TNF-α and IL-1β levels were determined by the ELISA. Immunohistochemical analyzes for MMP-9, COX-2 and TGF-β, immunofluorescence for iNOS and NF-κB/p65, protein expression for SMAD 2/3 by Western blot and RT-PCR for STAT1, PPAR-γ and NF-κB/p65 were performed. Blood samples were used to evaluate hepatic and renal function as well as for leukocyte count. The results showed that Telmisartan at doses of 5 or 10 mg/Kg prevented the inflammatory effects of OM, with a decrease in macroscopic and histopathological (p < 0,05) and proinflammatory cytokine levels TNF-α and IL-1β (p < 0,05). TELM at the dose of 10 mg/Kg decreased the immunostaining for MMP-9, COX-2 and TGF-β, reduced immunoexpression for iNOS and NF-κB/p65 and protein expression of SMAD 2/3. TELM at doses of 5 or 10 mg/Kg reduced the gene expression of STAT1 and NF-κB/p65 and increased PPAR-γ expression, compared to the 5-FU group. The groups treated with TELM at doses of 1, 5 or 10 mg/Kg did not show significant difference (p < 0,05) in liver and renal function levels and showed a decrease in the number of leukocytes when compared to the 5-FU group. Thus, the drug Telmisartan had a protective effect on MO induced in hamsters, however, further studies are still needed. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A mucosite oral (MO) é um efeito colateral debilitante frequentemente presente nos pacientes em tratamento de câncer, que afeta a cavidade oral ou orofaringe. As lesões resultantes da MO podem comprometer a qualidade de vida dos pacientes submetidos a radioterapia e/ou a quimioterapia, bem como contribuir na suspensão do protocolo do tratamento do câncer. Este estudo tem como objetivo avaliar os efeitos anti-inflamatórios da Telmisartana (TELM), um antagonista do receptor de angiotensina II, em um modelo experimental de mucosite oral induzido pelo quimioterápico 5-fluorouracil (5-FU) em hamsters. No decorrer de 10 dias, grupos de animais que foram submetidos ao 5-FU, foram tratados com telmisartana nas doses de 1, 5 ou 10mg/Kg. Os animais receberam injeção intraperitoneal de 5-fluorouracil no 1° e 2° dia, nas doses de 60 e 40mg/Kg, respectivamente, e tiveram a sua bolsa jugal direita evertida e arranhada superficialmente no 4° dia. Os animais foram eutanasiados no 10° dia e amostras de sangue e das mucosas foram coletadas. As mucosas foram avaliadas clinicamente, por meio da atribuição de escores após análises macroscópica e histopatológica. Os níveis de TNF-α e IL-1β foram determinados pelo ELISA. Foram realizadas análises por imunohistoquímica para MMP-9, COX-2 e TGF-β, imunofluorescência para NOSi e NF-κB/p65, expressão proteica para SMAD 2/3 por Western blot e RT-PCR para STAT1, PPAR-γ e NF-κB/p65. As amostras de sangue foram utilizadas para avaliação da função hepática e renal, bem como para a contagem de leucócitos. Os resultados demonstraram que a Telmisartana na dose de 5 ou 10 mg/Kg preveniu os efeitos inflamatórios da MO, com diminuição dos escores macroscópicos e histopatológicos (p < 0,05) e níveis de citocinas pró-inflamatórias TNF-α e IL-1β (p < 0,05). A TELM na dose de 10 mg/Kg diminuiu a imunomarcação para MMP-9, COX-2 e TGF-β, reduziu a imunoexpressão para NOSi e NF-κB/p65 e a expressão proteica de SMAD 2/3. TELM nas doses de 5 ou 10 mg/Kg reduziu a expressão gênica do STAT1 e NF-κB/p65 e aumentou a expressão do PPAR-γ, comparado com o grupo 5-FU. Os grupos tratados com TELM nas doses de 1, 5 ou 10mg/Kg não apresentaram diferença significativa (p < 0,05) nos níveis das funções hepática e renal e demonstraram diminuição no número de leucócitos quando comparados com o grupo 5-FU. Assim sendo, o fármaco Telmisartana teve um efeito protetor na MO induzida em hamsters, porém, mais estudos ainda são necessários. 2018-05-09T20:29:29Z 2018-05-09T20:29:29Z 2018-02-02 masterThesis BARBOSA, Maisie Mitchele. Efeito da telmisartana no modelo de mucosite oral induzida por 5-Fluorouracil em hamsters Golden Syriam (Mesocricetus auratus). 2018. 86f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2018. https://repositorio.ufrn.br/jspui/handle/123456789/25147 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS BIOLÓGICAS

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