Avaliação dos mecanismos bioquímicos, celulares e moleculares na cicatrização de lesões cutâneas em ratos utilizando cremes à base de extrato hidroalcoólico e óleo-resina de Copaifera langsdorffii
Carregando...
Data
2017-02-23
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
A pele é fundamental para manter a integridade do organismo e a descontinuidade desse sistema promove o mecanismo cicatricial, processo fisiológico que pode ser dividido em fase inflamatória, proliferativa e de remodelamento. As lesões cutâneas têm grande importância no investimento de recursos públicos devido à possibilidade de algum tipo de deficiência física ou até mesmo levar à morte. A Copaifera langsdorffii Desf. (Leguminosae) é uma árvore que, segundo conhecimento popular, apresenta atividades anti-inflamatória, antimicrobiana e de cicatrização de feridas. Sendo assim, o projeto teve por objetivo investigar o potencial cicatrizante dos cremes à base de extrato hidroalcoólico das folhas (10% EH) ou óleo-resina das cascas (10% OR) de Copaifera langsdorffii em feridas cutâneas de ratos e os mecanismos envolvidos. Ratos Wistar machos foram randomicamente divididos em quatro grupos experimentais (n = 8): creme base lanette (controle negativo - veículo), creme Collagenase 1.2 UI (controle positivo), cremes 10% EH ou 10% OR. Os animais foram submetidos à anestesia e indução da lesão dorsal de 2 cm de diâmetro. As lesões foram tratadas uma vez por dia e tiveram a área medida durante 3, 7 e 14 dias. Após a eutanásia, a região da ferida foi destinada a análises moleculares, histológicas, imunohistoquímicas e determinação de atividade anti-inflamatória local. Nossos resultados mostram o potencial cicatricial dos tratamentos 10% EH e 10% OR, com a significativa retração das lesões comparadas ao grupo Lanette. Os tratamentos à base de copaíba apresentaram atividade anti-inflamatória, com redução de citocinas pró-inflamatórias e aumento da citocina anti-inflamatória IL-10. Os resultados moleculares e imunohistoquímicos mostraram a atividade dos tratamentos 10% EH e 10% OR nos mecanismos de proliferação celular, angiogênese estimulada por VEGF, reepitelização mediada por EGF, MMP-2 e MMP-9, retração da lesão estimulada pelo MIF e remodelação das fibras colágenas. Desse modo, os tratamentos 10% EH e 10% OR apresentaram grande potencial na cicatrização de lesões cutâneas, com resultados melhores que o fármaco de referência na de proliferação, angiogênese e retração da lesão e apresentando resultados semelhantes ao fármaco na reepitelização e remodelamento de matriz, demonstrando potencial na cicatrização de lesões de pele.
The skin is fundamental to maintain the integrity of the body and the disruption of this system promotes the wound healing mechanism, physiological process that can be divided into inflammatory, proliferative and remodeling phases. The skin wounds have great importance in the investment of public resources due to the possibility of some type of physical disability or even death. The Copaifera langsdorffii Desf. (Leguminosae) is a tree that, according to popular knowledge, has anti-inflammatory, antimicrobial and wound healing activities. Therefore, the aim of this study was to investigate the healing potential of the ointments containing hydroalcoholic extracts of the leaves (10% EH) or oleoresin of the bark (10% OR) of Copaifera langsdorffii in cutaneous wounds of rats and the mechanisms involved. Male Wistar rats were randomly divided into four experimental groups (n = 8): lanette ointment (negative control - vehicle), Collagenase 1.2 IU ointment (positive control), 10% EH or 10% OR ointments. The animals were submitted to anesthesia and induction of the dorsal lesion of 2 cm in diameter. The lesions were treated once a day and had their areas measured for 3, 7 and 14 days. After euthanasia, the wounds were assigned to molecular, histological, immunohistochemical analysis and determination of the local anti-inflammatory activity. Our results show the healing potential of treatments 10% EH and 10% OR, with significant retraction of the wounds compared to the Lanette group. The copaiba-based treatments showed anti-inflammatory activity, with reduction of pro-inflammatory cytokines and increase of the anti-inflammatory cytokine IL-10. Molecular and immunohistochemical results showed the activity of 10% EH and 10% OR in the mechanisms of cell proliferation, VEGF-stimulated angiogenesis, reepithelialization mediated by EGF, MMP-2 and MMP-9, MIF-stimulated wound retraction and remodeling of collagen fibers. Thus, the treatments 10% EH and 10% OR presented great potential in skin wound healing, with better results than the reference drug in the proliferation, angiogenesis and retraction of the lesion and presenting similar results as the reference drug in reepithelialization and remodeling, with great potential in the skin wound healing.
The skin is fundamental to maintain the integrity of the body and the disruption of this system promotes the wound healing mechanism, physiological process that can be divided into inflammatory, proliferative and remodeling phases. The skin wounds have great importance in the investment of public resources due to the possibility of some type of physical disability or even death. The Copaifera langsdorffii Desf. (Leguminosae) is a tree that, according to popular knowledge, has anti-inflammatory, antimicrobial and wound healing activities. Therefore, the aim of this study was to investigate the healing potential of the ointments containing hydroalcoholic extracts of the leaves (10% EH) or oleoresin of the bark (10% OR) of Copaifera langsdorffii in cutaneous wounds of rats and the mechanisms involved. Male Wistar rats were randomly divided into four experimental groups (n = 8): lanette ointment (negative control - vehicle), Collagenase 1.2 IU ointment (positive control), 10% EH or 10% OR ointments. The animals were submitted to anesthesia and induction of the dorsal lesion of 2 cm in diameter. The lesions were treated once a day and had their areas measured for 3, 7 and 14 days. After euthanasia, the wounds were assigned to molecular, histological, immunohistochemical analysis and determination of the local anti-inflammatory activity. Our results show the healing potential of treatments 10% EH and 10% OR, with significant retraction of the wounds compared to the Lanette group. The copaiba-based treatments showed anti-inflammatory activity, with reduction of pro-inflammatory cytokines and increase of the anti-inflammatory cytokine IL-10. Molecular and immunohistochemical results showed the activity of 10% EH and 10% OR in the mechanisms of cell proliferation, VEGF-stimulated angiogenesis, reepithelialization mediated by EGF, MMP-2 and MMP-9, MIF-stimulated wound retraction and remodeling of collagen fibers. Thus, the treatments 10% EH and 10% OR presented great potential in skin wound healing, with better results than the reference drug in the proliferation, angiogenesis and retraction of the lesion and presenting similar results as the reference drug in reepithelialization and remodeling, with great potential in the skin wound healing.
Descrição
Palavras-chave
Cicatrização de lesões, Pele, Copaifera langsdorffii