Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele

Detalhes bibliográficos
Autor(a) principal: Pegoraro, Natháli Schopf
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/23585
Resumo: The skin, as an interface space between the environment and the body, is constantly exposed to harmful effects from the external environment, which are capable of evoking an inflammatory response. Since the treatment for skin inflammation has limitations due to the severity of the adverse effects caused, there is a constant need in the world scenario regarding the development of therapeutic alternatives to treat these affections. In this study, we developed formulations for the topical application of oleic acid (OA), a compound known to modulate mechanisms adjacent to wound healing. The first chapter of this thesis addresses the development of formulations based on Lanette® and Pemulen® TR2 containing OA and the evaluation of the anti-inflammatory effect of these formulations in a skin burn model in Swiss mice. Both formulations containing 3% OA inhibited the ultraviolet B (UVB) radiation-induced ear edema after single treatment (Imax = 79.36 ± 7.47% and 92.58 ± 2.58%, respectively). Pemulen® TR2 3% OA reduced inflammatory cell infiltration (Imax = 46.7 ± 4.0%) and ear edema after repeated treatment (Imax = 69.88 ± 2.31%; 60.95 ± 5.70% e 29.89 ± 6.40% at 24 h, 48 h and 72 h after UVB). In the second chapter, we verified that Pemulen® TR2 3% OA was able to inhibit the ear edema (Imax = 76.41 ± 5.69%), the infiltration of inflammatory cells (assessed by myeloperoxidase enzyme activity) (Imax = 71.37 ± 10.97%) and the level of the inflammatory cytokine interleukin (IL)-1β (Imax = 94.18 ± 12.03%) induced by croton oil in mice. Pemulen® TR2 3% OA inhibited ear edema in a model of persistent inflammation caused by successive croton oil administrations (Imax = 85.75 ± 3.08%), as well as inhibiting IL-1β-induced ear edema (Imax = 80.58 ± 2.45%). In both experimental models, we observed that the antiedematogenic effect is due, at least in part, to the action of OA on glucocorticoid receptors, since this effect was prevented by the glucocorticoid receptor antagonist mifepristone. This anti-inflammatory effect of Pemulen® TR2 3% OA was not associated with the occurrence of adverse effects usually caused by the use of glucocorticoids. These results suggest that the semisolids developed could be promising alternatives to treat inflammatory skin lesions. An alternative to improve treatment efficacy and limit the occurrence of adverse effects is the use of Nanotechnology. In this sense, a perspective for the conclusion of this study is. the association of OA and dexamethasone into nanostructured systems, benefiting from their advantages for the delivery of the active molecules, in order to propose a potential therapy to treat cutaneous inflammatory disorders.
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spelling 2022-01-19T16:47:06Z2022-01-19T16:47:06Z2021-08-12http://repositorio.ufsm.br/handle/1/23585The skin, as an interface space between the environment and the body, is constantly exposed to harmful effects from the external environment, which are capable of evoking an inflammatory response. Since the treatment for skin inflammation has limitations due to the severity of the adverse effects caused, there is a constant need in the world scenario regarding the development of therapeutic alternatives to treat these affections. In this study, we developed formulations for the topical application of oleic acid (OA), a compound known to modulate mechanisms adjacent to wound healing. The first chapter of this thesis addresses the development of formulations based on Lanette® and Pemulen® TR2 containing OA and the evaluation of the anti-inflammatory effect of these formulations in a skin burn model in Swiss mice. Both formulations containing 3% OA inhibited the ultraviolet B (UVB) radiation-induced ear edema after single treatment (Imax = 79.36 ± 7.47% and 92.58 ± 2.58%, respectively). Pemulen® TR2 3% OA reduced inflammatory cell infiltration (Imax = 46.7 ± 4.0%) and ear edema after repeated treatment (Imax = 69.88 ± 2.31%; 60.95 ± 5.70% e 29.89 ± 6.40% at 24 h, 48 h and 72 h after UVB). In the second chapter, we verified that Pemulen® TR2 3% OA was able to inhibit the ear edema (Imax = 76.41 ± 5.69%), the infiltration of inflammatory cells (assessed by myeloperoxidase enzyme activity) (Imax = 71.37 ± 10.97%) and the level of the inflammatory cytokine interleukin (IL)-1β (Imax = 94.18 ± 12.03%) induced by croton oil in mice. Pemulen® TR2 3% OA inhibited ear edema in a model of persistent inflammation caused by successive croton oil administrations (Imax = 85.75 ± 3.08%), as well as inhibiting IL-1β-induced ear edema (Imax = 80.58 ± 2.45%). In both experimental models, we observed that the antiedematogenic effect is due, at least in part, to the action of OA on glucocorticoid receptors, since this effect was prevented by the glucocorticoid receptor antagonist mifepristone. This anti-inflammatory effect of Pemulen® TR2 3% OA was not associated with the occurrence of adverse effects usually caused by the use of glucocorticoids. These results suggest that the semisolids developed could be promising alternatives to treat inflammatory skin lesions. An alternative to improve treatment efficacy and limit the occurrence of adverse effects is the use of Nanotechnology. In this sense, a perspective for the conclusion of this study is. the association of OA and dexamethasone into nanostructured systems, benefiting from their advantages for the delivery of the active molecules, in order to propose a potential therapy to treat cutaneous inflammatory disorders.A pele, espaço de interface entre o ambiente e o corpo, está constantemente exposta a efeitos deletérios provenientes do meio externo, os quais são capazes de evocar uma resposta inflamatória. Uma vez que o tratamento para inflamação de pele apresenta limitações devido aos graves efeitos adversos causados, há uma necessidade constante no cenário mundial acerca do desenvolvimento de alternativas terapêuticas para tratar estes acometimentos. Neste trabalho foram desenvolvidas formulações para aplicação tópica do ácido oleico (AO), conhecido por modular mecanismos adjacentes à cicatrização de feridas. O primeiro capítulo desta tese aborda o desenvolvimento de formulações Lanette® e Pemulen® TR2 contendo AO e a avaliação do seu efeito anti-inflamatório em um modelo de queimadura de pele em camundongos Swiss. Ambas as formulações contendo 3% de AO inibiram o edema de orelha induzido pela radiação ultravioleta B (UVB) após tratamento único (Imáx = 79,36 ± 7,47% e 92,58 ± 2,58%, respectivamente). Pemulen® TR2 3% AO reduziu a infiltração de células inflamatórias (Imáx = 46,7 ± 4,0%) e o edema de orelha após tratamento repetido (Imáx = 69,88 ± 2,31%; 60,95 ± 5,70% e 29,89 ± 6,40% em 24 h, 48 h e 72 h após UVB). No segundo capítulo, verificamos que Pemulen® TR2 3% AO foi capaz de inibir o edema de orelha (Imáx = 76,41 ± 5,69%), a infiltração de células inflamatórias (avaliada pela atividade da enzima mieloperoxidase) (Imáx = 71,37 ± 10,97%) e o nível da citocina inflamatória interleucina (IL)-1β (Imáx = 94,18 ± 12,03%) induzidos por óleo de cróton em camundongos. Pemulen® TR2 3% AO inibiu o edema de orelha em um modelo de inflamação persistente causada por sucessivas administrações de óleo de cróton (Imáx = 85,75 ± 3,08%), assim como inibiu o edema de orelha induzido por IL-1β (Imáx = 80,58 ± 2,45%). Em ambos os modelos experimentais, observamos que o efeito antiedematogênico deve-se, pelo menos em parte, à ação do AO em receptores glicocorticoides, uma vez que este efeito foi prevenido pelo antagonista dos receptores glicocorticoides mifepristona. Este efeito anti-inflamatório do Pemulen® TR2 3% AO não esteve associado à ocorrência de efeitos adversos geralmente ocasionados pelo uso de glicocorticoides. Estes resultados sugerem que os semissólidos desenvolvidos poderiam constituir alternativas terapêuticas promissoras para tratar lesões inflamatórias de pele. Uma alternativa para melhorar a eficácia do tratamento e limitar a ocorrência de efeitos adversos é o emprego da Nanotecnologia. Por isso, temos como perspectiva para a conclusão deste trabalho, associar o AO à dexametasona em sistemas nanoestruturados, valendo-se das vantagens destes sistemas para a veiculação de ativos, a fim de propor uma terapia com potencial para tratar alterações cutâneas inflamatórias.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessÁcido oleicoAcetato de dexametasonaCorticosteroidesNanopartículasAnti-inflamatórioOleic acidDexamethasone acetateCorticosteroidsNanoparticlesAnti-inflammatoryCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de peleAnti-inflammatory effect of formulations for topical application of oleic acid and dexamethasone acetate in experimental models of skin inflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisOliveira, Sara Marchesan dehttp://lattes.cnpq.br/6574555059806902Cruz, Letíciahttp://lattes.cnpq.br/3095970241017527Adams, Andréa Inês HornSilva, Cássia Regina daColomé, Letícia MarquesBrucker, Natáliahttp://lattes.cnpq.br/5327108689800269Pegoraro, Natháli Schopf2008000000026002f2fa82b-4312-45cb-99e1-777746963f4b8ff35be3-74a3-4bc4-9471-463f640da36643e0c580-2b46-47a2-b8eb-87bb1c7308151bddc938-348f-44e7-919d-e3e933fd0808abcc1b60-51a7-4115-8e9a-bc8554624b33d0cc4596-9954-474f-9cb0-8940f784119be2423ca5-c34e-47af-98a6-ba143d378dfareponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
dc.title.alternative.eng.fl_str_mv Anti-inflammatory effect of formulations for topical application of oleic acid and dexamethasone acetate in experimental models of skin inflammation
title Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
spellingShingle Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
Pegoraro, Natháli Schopf
Ácido oleico
Acetato de dexametasona
Corticosteroides
Nanopartículas
Anti-inflamatório
Oleic acid
Dexamethasone acetate
Corticosteroids
Nanoparticles
Anti-inflammatory
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
title_full Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
title_fullStr Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
title_full_unstemmed Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
title_sort Efeito anti-inflamatório de formulações para aplicação tópica de ácido oleico e acetato de dexametasona em modelos experimentais de inflamação de pele
author Pegoraro, Natháli Schopf
author_facet Pegoraro, Natháli Schopf
author_role author
dc.contributor.advisor1.fl_str_mv Oliveira, Sara Marchesan de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6574555059806902
dc.contributor.advisor-co1.fl_str_mv Cruz, Letícia
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/3095970241017527
dc.contributor.referee1.fl_str_mv Adams, Andréa Inês Horn
dc.contributor.referee2.fl_str_mv Silva, Cássia Regina da
dc.contributor.referee3.fl_str_mv Colomé, Letícia Marques
dc.contributor.referee4.fl_str_mv Brucker, Natália
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5327108689800269
dc.contributor.author.fl_str_mv Pegoraro, Natháli Schopf
contributor_str_mv Oliveira, Sara Marchesan de
Cruz, Letícia
Adams, Andréa Inês Horn
Silva, Cássia Regina da
Colomé, Letícia Marques
Brucker, Natália
dc.subject.por.fl_str_mv Ácido oleico
Acetato de dexametasona
Corticosteroides
Nanopartículas
Anti-inflamatório
topic Ácido oleico
Acetato de dexametasona
Corticosteroides
Nanopartículas
Anti-inflamatório
Oleic acid
Dexamethasone acetate
Corticosteroids
Nanoparticles
Anti-inflammatory
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Oleic acid
Dexamethasone acetate
Corticosteroids
Nanoparticles
Anti-inflammatory
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description The skin, as an interface space between the environment and the body, is constantly exposed to harmful effects from the external environment, which are capable of evoking an inflammatory response. Since the treatment for skin inflammation has limitations due to the severity of the adverse effects caused, there is a constant need in the world scenario regarding the development of therapeutic alternatives to treat these affections. In this study, we developed formulations for the topical application of oleic acid (OA), a compound known to modulate mechanisms adjacent to wound healing. The first chapter of this thesis addresses the development of formulations based on Lanette® and Pemulen® TR2 containing OA and the evaluation of the anti-inflammatory effect of these formulations in a skin burn model in Swiss mice. Both formulations containing 3% OA inhibited the ultraviolet B (UVB) radiation-induced ear edema after single treatment (Imax = 79.36 ± 7.47% and 92.58 ± 2.58%, respectively). Pemulen® TR2 3% OA reduced inflammatory cell infiltration (Imax = 46.7 ± 4.0%) and ear edema after repeated treatment (Imax = 69.88 ± 2.31%; 60.95 ± 5.70% e 29.89 ± 6.40% at 24 h, 48 h and 72 h after UVB). In the second chapter, we verified that Pemulen® TR2 3% OA was able to inhibit the ear edema (Imax = 76.41 ± 5.69%), the infiltration of inflammatory cells (assessed by myeloperoxidase enzyme activity) (Imax = 71.37 ± 10.97%) and the level of the inflammatory cytokine interleukin (IL)-1β (Imax = 94.18 ± 12.03%) induced by croton oil in mice. Pemulen® TR2 3% OA inhibited ear edema in a model of persistent inflammation caused by successive croton oil administrations (Imax = 85.75 ± 3.08%), as well as inhibiting IL-1β-induced ear edema (Imax = 80.58 ± 2.45%). In both experimental models, we observed that the antiedematogenic effect is due, at least in part, to the action of OA on glucocorticoid receptors, since this effect was prevented by the glucocorticoid receptor antagonist mifepristone. This anti-inflammatory effect of Pemulen® TR2 3% OA was not associated with the occurrence of adverse effects usually caused by the use of glucocorticoids. These results suggest that the semisolids developed could be promising alternatives to treat inflammatory skin lesions. An alternative to improve treatment efficacy and limit the occurrence of adverse effects is the use of Nanotechnology. In this sense, a perspective for the conclusion of this study is. the association of OA and dexamethasone into nanostructured systems, benefiting from their advantages for the delivery of the active molecules, in order to propose a potential therapy to treat cutaneous inflammatory disorders.
publishDate 2021
dc.date.issued.fl_str_mv 2021-08-12
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Centro de Ciências Naturais e Exatas
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dc.publisher.initials.fl_str_mv UFSM
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Bioquímica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
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