Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | https://tede2.pucrs.br/tede2/handle/tede/10405 |
Resumo: | Oral mucositis (OM) is an acute and frequent adverse effect of antineoplastic therapy. This disorder deserves significant attention, as it affects the quality of life of patients and can become a limiting factor to treatment. Management of OM includes therapeutic interventions aimed at preventing and treating injuries. In the first article of this dissertation, a literature review was carried out, investigating the properties of polyphenols derived from Olea Europaea L. and their potential for the treatment of OM. Studies have shown that oleuropein, hydroxytyrosol (HT) and tyrosol modulate the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2), which are directly associated with development inflammatory diseases. In addition, polyphenols showed antioxidant and antimicrobial activity, demonstrated in vitro and in vivo. The second article describes an experimental study that evaluated the topical and systemic effect of HT in ulcerated lesions, mechanically induced on the tongue of mice treated with 5-fluourouracil (5-FU). Fifty-nine male mice received injections of 5-FU (days 0, 2 and 4), in addition to trauma to the ventral toungue (bottom surface of the tongue) (days 3, 4 and 5). All groups, except the control, were treated with 5-FU. The animals received the respective treatments, daily, according to the distribution of the groups: control group (saline), group 5-FU (saline), glycerin group (topically applied glycerin, and saline), systemic HT group (hydroxytyrosol 10 mg/kg), Oli Ola® group (3% hydroxytyrosol, 10mg/kg) and topical HT group (5% concentration, applied in topical form). The animals were euthanized after nine days of treatment. Clinical and histological analyzes of the oral mucosa were performed, in addition to evaluation of the myeloperoxidase (in the intenstine) and glutathione (in the liver) enzymes. The weight of the systemic HT group was significantly lower (P = 0.000) than that of the control group at the end of the study. In the clinical evaluation of the oral mucosa, no clinical signs of oral mucositis were observed and the ulcerated lesions were healed. In the histological evaluation of the tongue, in previously ulcerated regions, there was no difference between the groups regarding the inflammation scores (P = 0.139). The group that received treatment with HT in topical form presented all epithelialized samples, differing significantly from the group 5-FU (P = 0.012). The levels of the myeloperoxidase and glutathione enzymes did not differ significantly between the groups (P = 0.837 and 0.748, respectively). This study demonstrated that treatment with HT did not have positive effects on the healing of ulcerated oral lesions in animals treated with 5-FU. The HT did not reduce the intensity of the inflammatory process in the lesions, nor did it alter markers of intestinal inflammation or oxidative stress in the model used. In topical form, HT had a beneficial effect on the epithelial tissue, favoring the epithelialization of wounds. It is suggested to investigate this substance in topical form in other models of oral mucositis. |
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Salum, Fernanda Gonçalveshttp://lattes.cnpq.br/8451371491580538http://lattes.cnpq.br/3291908457072735Ribeiro, Alice2022-08-30T17:12:58Z2021-03-29https://tede2.pucrs.br/tede2/handle/tede/10405Oral mucositis (OM) is an acute and frequent adverse effect of antineoplastic therapy. This disorder deserves significant attention, as it affects the quality of life of patients and can become a limiting factor to treatment. Management of OM includes therapeutic interventions aimed at preventing and treating injuries. In the first article of this dissertation, a literature review was carried out, investigating the properties of polyphenols derived from Olea Europaea L. and their potential for the treatment of OM. Studies have shown that oleuropein, hydroxytyrosol (HT) and tyrosol modulate the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2), which are directly associated with development inflammatory diseases. In addition, polyphenols showed antioxidant and antimicrobial activity, demonstrated in vitro and in vivo. The second article describes an experimental study that evaluated the topical and systemic effect of HT in ulcerated lesions, mechanically induced on the tongue of mice treated with 5-fluourouracil (5-FU). Fifty-nine male mice received injections of 5-FU (days 0, 2 and 4), in addition to trauma to the ventral toungue (bottom surface of the tongue) (days 3, 4 and 5). All groups, except the control, were treated with 5-FU. The animals received the respective treatments, daily, according to the distribution of the groups: control group (saline), group 5-FU (saline), glycerin group (topically applied glycerin, and saline), systemic HT group (hydroxytyrosol 10 mg/kg), Oli Ola® group (3% hydroxytyrosol, 10mg/kg) and topical HT group (5% concentration, applied in topical form). The animals were euthanized after nine days of treatment. Clinical and histological analyzes of the oral mucosa were performed, in addition to evaluation of the myeloperoxidase (in the intenstine) and glutathione (in the liver) enzymes. The weight of the systemic HT group was significantly lower (P = 0.000) than that of the control group at the end of the study. In the clinical evaluation of the oral mucosa, no clinical signs of oral mucositis were observed and the ulcerated lesions were healed. In the histological evaluation of the tongue, in previously ulcerated regions, there was no difference between the groups regarding the inflammation scores (P = 0.139). The group that received treatment with HT in topical form presented all epithelialized samples, differing significantly from the group 5-FU (P = 0.012). The levels of the myeloperoxidase and glutathione enzymes did not differ significantly between the groups (P = 0.837 and 0.748, respectively). This study demonstrated that treatment with HT did not have positive effects on the healing of ulcerated oral lesions in animals treated with 5-FU. The HT did not reduce the intensity of the inflammatory process in the lesions, nor did it alter markers of intestinal inflammation or oxidative stress in the model used. In topical form, HT had a beneficial effect on the epithelial tissue, favoring the epithelialization of wounds. It is suggested to investigate this substance in topical form in other models of oral mucositis.A mucosite oral (MO) é um efeito adverso agudo e frequente da terapia antineoplásica, que merece significativa atenção, pois afeta a qualidade de vida dos pacientes e pode tornar-se um fator limitante ao tratamento. O manejo da MO inclui intervenções terapêuticas direcionadas à prevenção e tratamento das lesões. No primeiro artigo desta dissertação, foi realizada uma revisão da literatura, investigando as propriedades dos polifenóis derivados da Olea Europaea L. e seu potencial uso terapêutico para o tratamento da MO. Os estudos demonstraram que a oleuropeína, o hidroxitirosol (HT) e o tirosol modulam a liberação de citocinas pró-inflamatórias como o fator de necrose tumoral alfa (TNF-α) e a ciclooxigenase-2 (COX-2), diretamente associadas ao desenvolvimento de doenças inflamatórias. Além disso, os polifenóis apresentaram atividade antioxidante e antimicrobiana, demonstrada in vitro e in vivo. O segundo artigo descreve um estudo experimental que avaliou o efeito tópico e sistêmico do HT em lesões ulceradas, mecanicamente induzidas na língua de camundongos tratados com 5-fluourouracil (5-FU). Cinquenta e nove camundongos machos receberam injeções de 5-FU (dias 0, 2 e 4), além de trauma no ventre lingual (dias 3, 4 e 5). Todos os grupos, com exceção do controle, foram tratados com 5-FU. Os animais receberam os respectivos tratamentos, diariamente, conforme a distribuição dos grupos: grupo controle (solução salina), grupo 5-FU (solução salina), grupo glicerina (glicerina aplicada de forma tópica, e solução salina), grupo HT sistêmico (hidroxitirosol 10 mg/kg), grupo Oli Ola® (hidroxitirosol 3%, 10mg/kg) e grupo HT tópico (concentração de 5%, aplicado na forma tópica). Os animais foram eutanasiados após nove dias de tratamento. Foram realizadas análises clínica e histológica da mucosa bucal, além de avaliação das enzimas mieloperoxidase (no intenstino) e glutationa (no fígado). O peso do grupo HT sistêmico foi significativamente inferior (P= 0,000) ao do grupo controle ao final do estudo. Na avaliação clínica da mucosa bucal, não foram observados sinais clínicos de mucosite oral e as lesões ulceradas apresentaram-se cicatrizadas. Na avaliação histológica da língua, nas regiões previamente ulceradas, não houve diferença entre os grupos quanto aos escores de inflamação (P=0,139). O grupo que recebeu tratamento com HT na forma tópica apresentou todas as amostras epitelizadas, diferindo significativamente do grupo 5-FU (P= 0,012). Os níveis das enzimas mieloperoxidase e glutationa não diferiram significativamente entre os grupos (P= 0,837 e 0,748, respectivamente). Este estudo demonstrou que o tratamento com HT não apresentou efeitos positivos na cicatrização de lesões bucais ulceradas em animais tratados com 5-FU. O HT também não reduziu a intensidade do processo inflamatório nas lesões, nem alterou marcadores de inflamação intestinal ou de estresse oxidativo no modelo utilizado. Na forma tópica, o HT teve efeito benéfico sobre o tecido epitelial de revestimento, favorecendo a epitelização das feridas. Sugere-se a investigação dessa substância na forma tópica em outros modelos de mucosite oral.Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2022-08-29T13:22:00Z No. of bitstreams: 1 ALICE_RIBEIRO_DIS.pdf: 841042 bytes, checksum: f48639653c27a01884ca570d94db623b (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2022-08-30T17:06:51Z (GMT) No. of bitstreams: 1 ALICE_RIBEIRO_DIS.pdf: 841042 bytes, checksum: f48639653c27a01884ca570d94db623b (MD5)Made available in DSpace on 2022-08-30T17:12:58Z (GMT). No. of bitstreams: 1 ALICE_RIBEIRO_DIS.pdf: 841042 bytes, checksum: f48639653c27a01884ca570d94db623b (MD5) Previous issue date: 2021-03-29Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfhttps://tede2.pucrs.br/tede2/retrieve/185146/DIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em OdontologiaPUCRSBrasilEscola de Ciências Saúde e da VidaMucosite Oral5-FUPolifenóisHydroxytyrosolPolyphenolsOral Mucositis5-FUHydroxytyrosolCIENCIAS DA SAUDE::ODONTOLOGIAAvaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho será publicado como artigo ou livro60 meses30/08/2027-7411869720500764667500500600-20704984698792443491802873727776104890info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.jpgDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.jpgimage/jpeg4116https://tede2.pucrs.br/tede2/bitstream/tede/10405/4/DIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.jpg64e19aad9349c938ea7d8e7015b758e4MD54TEXTDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.txtDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.txttext/plain1762https://tede2.pucrs.br/tede2/bitstream/tede/10405/3/DIS_ALICE_RIBEIRO_CONFIDENCIAL.pdf.txtd39a009be88f771320a7407ab043a2a6MD53ORIGINALDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdfDIS_ALICE_RIBEIRO_CONFIDENCIAL.pdfapplication/pdf192457https://tede2.pucrs.br/tede2/bitstream/tede/10405/2/DIS_ALICE_RIBEIRO_CONFIDENCIAL.pdfeee961d5044bc575b1881d79cecd28a9MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590https://tede2.pucrs.br/tede2/bitstream/tede/10405/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/104052022-08-30 20:00:17.59oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2022-08-30T23:00:17Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
title |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
spellingShingle |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos Ribeiro, Alice Mucosite Oral 5-FU Polifenóis Hydroxytyrosol Polyphenols Oral Mucositis 5-FU Hydroxytyrosol CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
title_full |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
title_fullStr |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
title_full_unstemmed |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
title_sort |
Avaliação do efeito de polifenóis derivados da Olea Europaea L. na prevenção e tratamento da mucosite oral induzida por quimioterapia em camundongos |
author |
Ribeiro, Alice |
author_facet |
Ribeiro, Alice |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Salum, Fernanda Gonçalves |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8451371491580538 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3291908457072735 |
dc.contributor.author.fl_str_mv |
Ribeiro, Alice |
contributor_str_mv |
Salum, Fernanda Gonçalves |
dc.subject.por.fl_str_mv |
Mucosite Oral 5-FU Polifenóis |
topic |
Mucosite Oral 5-FU Polifenóis Hydroxytyrosol Polyphenols Oral Mucositis 5-FU Hydroxytyrosol CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Hydroxytyrosol Polyphenols Oral Mucositis 5-FU Hydroxytyrosol |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
Oral mucositis (OM) is an acute and frequent adverse effect of antineoplastic therapy. This disorder deserves significant attention, as it affects the quality of life of patients and can become a limiting factor to treatment. Management of OM includes therapeutic interventions aimed at preventing and treating injuries. In the first article of this dissertation, a literature review was carried out, investigating the properties of polyphenols derived from Olea Europaea L. and their potential for the treatment of OM. Studies have shown that oleuropein, hydroxytyrosol (HT) and tyrosol modulate the release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2), which are directly associated with development inflammatory diseases. In addition, polyphenols showed antioxidant and antimicrobial activity, demonstrated in vitro and in vivo. The second article describes an experimental study that evaluated the topical and systemic effect of HT in ulcerated lesions, mechanically induced on the tongue of mice treated with 5-fluourouracil (5-FU). Fifty-nine male mice received injections of 5-FU (days 0, 2 and 4), in addition to trauma to the ventral toungue (bottom surface of the tongue) (days 3, 4 and 5). All groups, except the control, were treated with 5-FU. The animals received the respective treatments, daily, according to the distribution of the groups: control group (saline), group 5-FU (saline), glycerin group (topically applied glycerin, and saline), systemic HT group (hydroxytyrosol 10 mg/kg), Oli Ola® group (3% hydroxytyrosol, 10mg/kg) and topical HT group (5% concentration, applied in topical form). The animals were euthanized after nine days of treatment. Clinical and histological analyzes of the oral mucosa were performed, in addition to evaluation of the myeloperoxidase (in the intenstine) and glutathione (in the liver) enzymes. The weight of the systemic HT group was significantly lower (P = 0.000) than that of the control group at the end of the study. In the clinical evaluation of the oral mucosa, no clinical signs of oral mucositis were observed and the ulcerated lesions were healed. In the histological evaluation of the tongue, in previously ulcerated regions, there was no difference between the groups regarding the inflammation scores (P = 0.139). The group that received treatment with HT in topical form presented all epithelialized samples, differing significantly from the group 5-FU (P = 0.012). The levels of the myeloperoxidase and glutathione enzymes did not differ significantly between the groups (P = 0.837 and 0.748, respectively). This study demonstrated that treatment with HT did not have positive effects on the healing of ulcerated oral lesions in animals treated with 5-FU. The HT did not reduce the intensity of the inflammatory process in the lesions, nor did it alter markers of intestinal inflammation or oxidative stress in the model used. In topical form, HT had a beneficial effect on the epithelial tissue, favoring the epithelialization of wounds. It is suggested to investigate this substance in topical form in other models of oral mucositis. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-03-29 |
dc.date.accessioned.fl_str_mv |
2022-08-30T17:12:58Z |
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https://tede2.pucrs.br/tede2/handle/tede/10405 |
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https://tede2.pucrs.br/tede2/handle/tede/10405 |
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por |
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por |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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PUCRS |
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Brasil |
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Escola de Ciências Saúde e da Vida |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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