Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | http://ri.ufs.br/jspui/handle/riufs/17164 |
Resumo: | The effectiveness of pharmacological therapy for the treatment of wounds is variable, as well as its side effects, which drives the search for new therapeutic modalities, among them products based on medicinal plants and nanotechnology. Chrysin, a flavonoid found in several plant species, has pharmacological properties such as: antioxidants, anti-inflammatories, antimicrobials, antibacterials and antiallergic agents that can contribute to an adequate scar repair. In this way, the work aimed to evaluate the effects of bioactive collagen membranes containing chrysin in liposomes on the healing of skin wounds in an animal model of excisional skin wounds. 72 rats (Wistar) and 18 male mice (Swiss) were used, submitted to a cutaneous excision and randomized in the groups according to treatment: without intervention - (SI); control - collagen membrane containing liposomes (COL) and collagen membrane containing chrysin in liposomes (COL / CRI) - patent filed with INPI BR 10 2019 018341 1. The experimental protocols were approved by CEPA / UFS (55/2018). Wound areas were measured using an 8 mm diameter digital caliper on the 3rd, 7th, 14th and 21st day postinjury and histologically evaluated (hematoxylin-eosin stain) for response and type of inflammatory infiltrate, granulation tissue, proliferation fibroblasts, deposition of collagen fibers and re-epithelialization in the healing area. The effect of membranes containing chrysin was evaluated for vascular endothelial growth factor (VEGF) and kappa nuclear factor B (NFkB) by Western blot, interleukins IL-1β and IL-6 by ELISA and SOD and CAT by the colorimetric method. Differences between groups were analyzed using the one-way ANOVA test, followed by the Tukey post-test. The results were expressed as mean ± E.P.M. and considered significant when p <0.05. The chrysin content in the membranes was 165.37 ± 11.70 μg · cm-2, obtaining an encapsulation efficiency of 87.82%. In the analysis of the wound reduction area, the animals treated with COL / CRI significantly increased the percentage of wound reduction on the 3rd day when compared to the SI group (p <0.05) and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In assessing the intensity of the inflammatory reaction, COL / CRI decreased the inflammatory profile on the 3rd and 7th day when compared to the SI (p <0.001) and COL (p <0.01) groups, respectively. In histomorphological analysis, COL / CRI significantly increased the rates of epithelialization of residual wounds on the 3rd day when compared to the SI (p <0.001) and COL (p <0.05) groups and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In the assessment of inflammatory activity on the 7th post-injury day, the COL / CRI group significantly decreased NFkB levels when compared to the SI group (p <0.05) and the levels of interleukins IL-1β and IL-6 ( p <0.001) when compared to the SI group (p <0.001). On the 7th post-injury day, COL / CRI significantly increased VEGF levels when compared to the SI (p <0.01) and COL (p <0.001) group. In the antioxidant evaluation on the 7th day after injury, COL / CRI significantly increased SOD levels when compared to the SI group (p <0.05) and CAT when compared to the SI group (p <0.001). It is concluded, therefore, that the membranes containing chrysin have antioxidant, anti-inflammatory, angiogenic and healing actions representing a promising biotechnological alternative with clinical application for the treatment of wounds. |
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Carvalho, Mikaella Tuanny BezerraBarreto, Rosana de Souza Siqueira2023-02-15T15:09:39Z2023-02-15T15:09:39Z2020CARVALHO, Mikaella Tuanny Bezerra. Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas. 2020. 118 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2020.http://ri.ufs.br/jspui/handle/riufs/17164The effectiveness of pharmacological therapy for the treatment of wounds is variable, as well as its side effects, which drives the search for new therapeutic modalities, among them products based on medicinal plants and nanotechnology. Chrysin, a flavonoid found in several plant species, has pharmacological properties such as: antioxidants, anti-inflammatories, antimicrobials, antibacterials and antiallergic agents that can contribute to an adequate scar repair. In this way, the work aimed to evaluate the effects of bioactive collagen membranes containing chrysin in liposomes on the healing of skin wounds in an animal model of excisional skin wounds. 72 rats (Wistar) and 18 male mice (Swiss) were used, submitted to a cutaneous excision and randomized in the groups according to treatment: without intervention - (SI); control - collagen membrane containing liposomes (COL) and collagen membrane containing chrysin in liposomes (COL / CRI) - patent filed with INPI BR 10 2019 018341 1. The experimental protocols were approved by CEPA / UFS (55/2018). Wound areas were measured using an 8 mm diameter digital caliper on the 3rd, 7th, 14th and 21st day postinjury and histologically evaluated (hematoxylin-eosin stain) for response and type of inflammatory infiltrate, granulation tissue, proliferation fibroblasts, deposition of collagen fibers and re-epithelialization in the healing area. The effect of membranes containing chrysin was evaluated for vascular endothelial growth factor (VEGF) and kappa nuclear factor B (NFkB) by Western blot, interleukins IL-1β and IL-6 by ELISA and SOD and CAT by the colorimetric method. Differences between groups were analyzed using the one-way ANOVA test, followed by the Tukey post-test. The results were expressed as mean ± E.P.M. and considered significant when p <0.05. The chrysin content in the membranes was 165.37 ± 11.70 μg · cm-2, obtaining an encapsulation efficiency of 87.82%. In the analysis of the wound reduction area, the animals treated with COL / CRI significantly increased the percentage of wound reduction on the 3rd day when compared to the SI group (p <0.05) and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In assessing the intensity of the inflammatory reaction, COL / CRI decreased the inflammatory profile on the 3rd and 7th day when compared to the SI (p <0.001) and COL (p <0.01) groups, respectively. In histomorphological analysis, COL / CRI significantly increased the rates of epithelialization of residual wounds on the 3rd day when compared to the SI (p <0.001) and COL (p <0.05) groups and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In the assessment of inflammatory activity on the 7th post-injury day, the COL / CRI group significantly decreased NFkB levels when compared to the SI group (p <0.05) and the levels of interleukins IL-1β and IL-6 ( p <0.001) when compared to the SI group (p <0.001). On the 7th post-injury day, COL / CRI significantly increased VEGF levels when compared to the SI (p <0.01) and COL (p <0.001) group. In the antioxidant evaluation on the 7th day after injury, COL / CRI significantly increased SOD levels when compared to the SI group (p <0.05) and CAT when compared to the SI group (p <0.001). It is concluded, therefore, that the membranes containing chrysin have antioxidant, anti-inflammatory, angiogenic and healing actions representing a promising biotechnological alternative with clinical application for the treatment of wounds.A eficácia da terapia farmacológica para o tratamento das feridas é variável, assim como seus efeitos colaterais, o que impulsiona a busca por novas modalidades terapêuticas, dentre elas os produtos com base em plantas medicinais e nanotecnologia. A crisina, um flavonoide encontrado em várias espécies de plantas apresenta propriedades farmacológicas tais como: antioxidantes, anti-inflamatórias, antimicrobianas, antibacterianas e antialérgicas que podem contribuir para um adequado reparo cicatricial. Desta forma, o trabalho objetivou avaliar os efeitos das membranas bioativas de colágeno contendo crisina em lipossomas sobre a cicatrização de feridas cutâneas em modelo animal de ferida cutânea excisional. Foram utilizados 72 Ratos (Wistar) e 18 camundongos (Swiss) machos, submetidos a uma excisão cutânea e randomizados nos grupos conforme tratamento: sem intervenção - (SI); controle - membrana de colágeno contendo lipossomas (COL) e membrana de colágeno contendo crisina em lipossomas (COL/CRI) – patente requerida junto ao INPI BR 10 2019 018341 1. Os protocolos experimentais foram aprovados pelo CEPA/UFS (55/2018). As áreas das feridas foram mensuradas através do paquímetro digital de 8 mm de diâmetro no 3º, 7º, 14º e 21º dia pós-lesão e avaliadas histologicamente (coloração hematoxilina-eosina) quanto à resposta e tipo de infiltrado inflamatório, tecido de granulação, proliferação de fibroblastos, deposição de fibras colágenas e reepitelização na área de cicatrização. O efeito das membranas contendo crisina foi avaliado quanto ao fator de crescimento endotelial vascular (VEGF) e fator nuclear kappa B (NFB) por Western blot, interleucinas IL-1β e IL-6 por ELISA e SOD e CAT pelo método colorimétrico. As diferenças entre os grupos foram analisadas por meio do teste ANOVA, uma via, seguido pelo pós- teste de Tukey. Os resultados foram expressos como média ± E.P.M. e considerados significativos quando p<0,05. O teor da crisina nas membranas foi de 165,37 ± 11,70 μg·cm-2, obtendo eficiência de encapsulação de 87,82%. Na análise da área de redução das feridas, os animais tratados com COL/CRI aumentaram significativamente o percentual de redução das feridas no 3º dia quando comparado ao grupo SI (p<0,05) e no 7º dia quando comparado aos grupos SI (p<0,001) e COL (p<0,01). Na avaliação da intensidade da reação inflamatória, COL/CRI diminuiu o perfil inflamatório no 3º e 7º dia quando comparado aos grupos SI (p<0,001) e COL (p<0,01) respectivamente. Na análise histomorfológica, COL/CRI aumentou significativamente as taxas de epitelização das feridas residuais no 3º dia quando com comparado aos grupos SI (p<0,001) e COL (p<0,05) e no 7º dia quando comparado aos grupos SI (p<0,001) e COL (p<0,01). Na avaliação da atividade inflamatória no 7º dia póslesão, o grupo COL/CRI diminuiu significativamente os níveis do NFB quando comparado ao grupo SI (p<0,05) e os níveis das interleucinas IL-1β e IL-6 (p<0,001) quando comparado ao grupo SI (p<0,001). No 7º dia pós- lesão, COL/CRI aumentou significativamente os níveis de VEGF quando comparado ao grupo SI (p<0,01) e COL (p<0,001). Na avaliação antioxidante no 7º dia pós- lesão, COL/CRI aumentou significativamente os níveis de SOD quando comparado ao grupo SI (p<0,05) e CAT quando comparado ao grupo SI (p<0,001). Conclui-se, assim, que as membranas contendo crisina apresentam ações antioxidantes, antiinflamatórias, angiogênicas e cicatrizantes representando uma alternativa biotecnológica promissora com aplicação clínica para o tratamento de feridas.AracajuporCicatrização de feridasColágenoCrisinaLipossomasFlavonaWound healingCollagenChrysinFlavoneLiposomesCIENCIAS DA SAUDEMembranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/17164/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdfMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdfapplication/pdf3464586https://ri.ufs.br/jspui/bitstream/riufs/17164/2/MIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf874a4ea1e1983123ff6f2185421c47d5MD52TEXTMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.txtMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.txtExtracted texttext/plain216919https://ri.ufs.br/jspui/bitstream/riufs/17164/3/MIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.txt828b8c89a0d1ca5859704b3de9fd0bd4MD53THUMBNAILMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.jpgMIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.jpgGenerated Thumbnailimage/jpeg1315https://ri.ufs.br/jspui/bitstream/riufs/17164/4/MIKAELLA_TUANNY_BEZERRA_CARVALHO.pdf.jpg9d5a09b5d167cccf9cef8134ae94e108MD54riufs/171642023-02-15 12:09:39.181oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2023-02-15T15:09:39Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
title |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
spellingShingle |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas Carvalho, Mikaella Tuanny Bezerra Cicatrização de feridas Colágeno Crisina Lipossomas Flavona Wound healing Collagen Chrysin Flavone Liposomes CIENCIAS DA SAUDE |
title_short |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
title_full |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
title_fullStr |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
title_full_unstemmed |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
title_sort |
Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas |
author |
Carvalho, Mikaella Tuanny Bezerra |
author_facet |
Carvalho, Mikaella Tuanny Bezerra |
author_role |
author |
dc.contributor.author.fl_str_mv |
Carvalho, Mikaella Tuanny Bezerra |
dc.contributor.advisor1.fl_str_mv |
Barreto, Rosana de Souza Siqueira |
contributor_str_mv |
Barreto, Rosana de Souza Siqueira |
dc.subject.por.fl_str_mv |
Cicatrização de feridas Colágeno Crisina Lipossomas Flavona |
topic |
Cicatrização de feridas Colágeno Crisina Lipossomas Flavona Wound healing Collagen Chrysin Flavone Liposomes CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Wound healing Collagen Chrysin Flavone Liposomes |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
The effectiveness of pharmacological therapy for the treatment of wounds is variable, as well as its side effects, which drives the search for new therapeutic modalities, among them products based on medicinal plants and nanotechnology. Chrysin, a flavonoid found in several plant species, has pharmacological properties such as: antioxidants, anti-inflammatories, antimicrobials, antibacterials and antiallergic agents that can contribute to an adequate scar repair. In this way, the work aimed to evaluate the effects of bioactive collagen membranes containing chrysin in liposomes on the healing of skin wounds in an animal model of excisional skin wounds. 72 rats (Wistar) and 18 male mice (Swiss) were used, submitted to a cutaneous excision and randomized in the groups according to treatment: without intervention - (SI); control - collagen membrane containing liposomes (COL) and collagen membrane containing chrysin in liposomes (COL / CRI) - patent filed with INPI BR 10 2019 018341 1. The experimental protocols were approved by CEPA / UFS (55/2018). Wound areas were measured using an 8 mm diameter digital caliper on the 3rd, 7th, 14th and 21st day postinjury and histologically evaluated (hematoxylin-eosin stain) for response and type of inflammatory infiltrate, granulation tissue, proliferation fibroblasts, deposition of collagen fibers and re-epithelialization in the healing area. The effect of membranes containing chrysin was evaluated for vascular endothelial growth factor (VEGF) and kappa nuclear factor B (NFkB) by Western blot, interleukins IL-1β and IL-6 by ELISA and SOD and CAT by the colorimetric method. Differences between groups were analyzed using the one-way ANOVA test, followed by the Tukey post-test. The results were expressed as mean ± E.P.M. and considered significant when p <0.05. The chrysin content in the membranes was 165.37 ± 11.70 μg · cm-2, obtaining an encapsulation efficiency of 87.82%. In the analysis of the wound reduction area, the animals treated with COL / CRI significantly increased the percentage of wound reduction on the 3rd day when compared to the SI group (p <0.05) and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In assessing the intensity of the inflammatory reaction, COL / CRI decreased the inflammatory profile on the 3rd and 7th day when compared to the SI (p <0.001) and COL (p <0.01) groups, respectively. In histomorphological analysis, COL / CRI significantly increased the rates of epithelialization of residual wounds on the 3rd day when compared to the SI (p <0.001) and COL (p <0.05) groups and on the 7th day when compared to the SI groups (p <0.001) and COL (p <0.01). In the assessment of inflammatory activity on the 7th post-injury day, the COL / CRI group significantly decreased NFkB levels when compared to the SI group (p <0.05) and the levels of interleukins IL-1β and IL-6 ( p <0.001) when compared to the SI group (p <0.001). On the 7th post-injury day, COL / CRI significantly increased VEGF levels when compared to the SI (p <0.01) and COL (p <0.001) group. In the antioxidant evaluation on the 7th day after injury, COL / CRI significantly increased SOD levels when compared to the SI group (p <0.05) and CAT when compared to the SI group (p <0.001). It is concluded, therefore, that the membranes containing chrysin have antioxidant, anti-inflammatory, angiogenic and healing actions representing a promising biotechnological alternative with clinical application for the treatment of wounds. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2023-02-15T15:09:39Z |
dc.date.available.fl_str_mv |
2023-02-15T15:09:39Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
CARVALHO, Mikaella Tuanny Bezerra. Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas. 2020. 118 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2020. |
dc.identifier.uri.fl_str_mv |
http://ri.ufs.br/jspui/handle/riufs/17164 |
identifier_str_mv |
CARVALHO, Mikaella Tuanny Bezerra. Membranas bioativas de colágeno contendo crisina em lipossomas reduz a inflamação e promove melhora na angiogênese e cicatrização de feridas cutâneas. 2020. 118 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2020. |
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http://ri.ufs.br/jspui/handle/riufs/17164 |
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Pós-Graduação em Ciências da Saúde |
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Universidade Federal de Sergipe |
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