1. Universidade Federal da Bahia
  2. Instituto de Ciências da Saúde (ICS)
  3. Programa de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular (PMBqBM)
  4. Dissertação (PMBqBM)
Use este identificador para citar ou linkar para este item: https://repositorio.ufba.br/handle/ri/39105
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Campo DCValorIdioma
dc.creatorCosta, Cinthia Cristina de Oliveira Santos-
dc.date.accessioned2024-02-27T15:31:14Z-
dc.date.available2024-02-27T15:31:14Z-
dc.date.issued2023-12-18-
dc.identifier.citationCOSTA, Cinthia Cristina de Oliveira Santos. Investigação dos efeitos da Apigenina conjugada a Ciclodextrinas em modelo in vitro de neuroinflamação em células da medula espinhal. 2023. 93 f. Dissertação (Mestrado) - Universidade Federal da Bahia, Instituto de Ciências da Saúde, Programa Multicêntrico de Pós-Graduação em Bioquímica e Biologia Molecular, Salvador, 2023.pt_BR
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/39105-
dc.description.abstractINTRODUCTION: Spinal cord injury is a serious damage to the central nervous system associated with high rates of morbidity and mortality, physical dependence, and financial burdens. Inflammation is the main characteristic of secondary injury that provides a cascade of cellular and molecular events that increase the area of injury, aggravating neurological deficits and tissue recovery. The literature presents different models of studies in the central nervous system in which apigenin has demonstrated beneficial effects. However, there is little research on the neuroprotective role of apigenin in spinal cord injury, and in addition, the low solubility of this flavonoid in water may be a limiting factor for its biological activities. Cyclodextrins are cyclic oligosaccharides whose chemical structure allows the incorporation of lipophilic substances in their cavity, giving these molecules greater stability and bioavailability. OBJECTIVE: To evaluate the anti-inflammatory and neuroprotective effect of flavonoid apigenin and conjugates of apigenin with β-cyclodextrins in an in vitro model of neuroinflammation in spinal cord cells. MATERIALS AND METHODS: In this work β-cyclodextrin (β-CD) and three other derivatives were used. The cytotoxicity of apigenin (API) and conjugates of apigenin with β-cyclodextrins (API-cd’s) was evaluated by MTT assay in PC-12 cells and spinal cord cells in a series of concentrations (0.1-100μM) for 24h. After its characterization, the primary culture of the spinal cord was submitted to inflammatory damage by LPS, and subsequently treated with apigenin and the best conjugates of apigenin. The investigation of changes in markers associated with neuroinflammation was performed by immunofluorescence. The nitric oxide production was analyzed with the supernatants of the experimental groups. The analysis of cell morphology was performed by phase contrast microscopy, Rosenfeld staining and immunofluorescence. Cell migration was evaluated by the wound healing assay and immunofluorescence. RESULTS AND DISCUSSION: The API and API-cd’s did not promote cytotoxic action in PC-12 cells at the concentrations tested. It was observed that three conjugates increased the viability of PC-12 cells, mainly at the concentration of 10μM. The API and API-cd’s did not induce cytotoxicity in primary culture of the spinal cord at the concentrations tested. The primary culture of spinal cord of neonate rats presents morphological diversity of astrocytes, microglia, and neurons, as well as cell growth clusters. Spinal cord cells were subjected to inflammatory damage by LPS at 5 μg/mL for 12 hours. The API and API-cd 52 decreased the expression of IBA-1 and CD-68-positive cells after LPS-induced damage. Two API-cd’s significantly reduced nitric oxide levels. Two API-cd’s significantly reduced the number of S100β-positive cells. CONCLUSIONS: Apigenin and apigenin conjugates appear to protect spinal cord cells in an in vitro model of neuroinflammation.pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)pt_BR
dc.description.sponsorshipPró-Reitoria de Pesquisa, Criação e Inovação (PROPCI) - Edital JOVEMPESQ – Edital PROPCI-PROPG/UFBA 007/202.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahiapt_BR
dc.subjectLesão medularpt_BR
dc.subjectTraumatismos da Medula Espinalpt_BR
dc.subjectApigeninapt_BR
dc.subjectNeuroproteçãopt_BR
dc.subject.otherspinal cord injurypt_BR
dc.subject.otherSpinal Cord Injuriespt_BR
dc.subject.otherApigeninpt_BR
dc.subject.otherNeuroprotectionpt_BR
dc.titleInvestigação dos efeitos da apigenina conjugada a ciclodextrinas em modelo in vitro de neuroinflamação em células da medula espinhalpt_BR
dc.typeDissertaçãopt_BR
dc.publisher.programPrograma de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular (PMBqBM) pt_BR
dc.publisher.initialsUFBApt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPQ::CIENCIAS BIOLOGICASpt_BR
dc.contributor.advisor1Nascimento, Ravena Pereira do-
dc.contributor.advisor1IDhttps://orcid.org/0000-0002-2915-3030pt_BR
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2974904635974456pt_BR
dc.contributor.advisor-co1Costa, Silvia Lima-
dc.contributor.advisor-co1IDhttps://orcid.org/0000-0002-8975-3871pt_BR
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/8965253841041518pt_BR
dc.contributor.referee1Nascimento, Ravena Pereira do-
dc.contributor.referee1IDhttps://orcid.org/0000-0002-2915-3030pt_BR
dc.contributor.referee1Latteshttp://lattes.cnpq.br/2974904635974456pt_BR
dc.contributor.referee2Santos, Balbino Lino dos-
dc.contributor.referee2IDhttps://orcid.org/0000-0002-6430-229Xpt_BR
dc.contributor.referee2Latteshttp://lattes.cnpq.br/3758218831795212pt_BR
dc.contributor.referee3Borges, Julita Maria Pereira-
dc.contributor.referee3IDhttps://orcid.org/0000-0003-3969-8146pt_BR
dc.contributor.referee3Latteshttp://lattes.cnpq.br/1160140281861469pt_BR
dc.creator.Latteshttps://lattes.cnpq.br/9580233863260982pt_BR
dc.description.resumoINTRODUÇÃO: A lesão medular é um grave dano ao sistema nervoso central associado a altas taxas de morbimortalidade, dependência física e encargos financeiros. A inflamação é a principal característica da lesão secundária que proporciona uma cascata de eventos celulares e moleculares que aumentam a área da lesão, agravando os déficits neurológicos e a recuperação tecidual. A literatura apresenta diferentes modelos de estudos no sistema nervoso central nos quais a apigenina tem demonstrado efeitos benéficos. No entanto, há poucas pesquisas sobre o papel neuroprotetor da apigenina na lesão medular, e, além disso, a baixa solubilidade desse flavonoide em água pode ser um fator limitante para suas atividades biológicas. As ciclodextrinas são oligossacarídeos cíclicos cuja estrutura química possibilita a incorporação de substâncias lipofílicas em sua cavidade, conferindo a essas moléculas maior estabilidade e biodisponibilidade. OBJETIVO: Avaliar o efeito anti-inflamatório e neuroprotetor do flavonoide apigenina e de conjugados de apigenina com β-ciclodextrinas em modelo in vitro de neuroinflamação em células da medula espinhal. MATERIAIS E MÉTODOS: Neste trabalho foram utilizadas β-ciclodextrina (β-CD) e outros três derivados. A citotoxicidade da apigenina (API) e dos conjugados de apigenina com β-ciclodextrinas (API-cd’s) foi avaliada pelo ensaio MTT em células PC-12 e células da medula espinhal em uma série de concentrações (0,1-100μM) por 24h. Após sua caracterização, a cultura primária da medula espinhal foi submetida ao dano inflamatório por LPS, e, posteriormente, tratada com apigenina e os melhores conjugados de apigenina. A investigação de alterações em marcadores associados à neuroinflamação foi feita por imunofluorescência. Realizou-se análise da produção de óxido nítrico com os sobrenadantes dos grupos experimentais. A análise da morfologia celular foi realizada por microscopia de contraste de fase, coloração de Rosenfeld e imunofluorescência. A migração celular foi avaliada a partir do ensaio de ranhura e imunofluorescência. RESULTADOS E DISCUSSÃO: A API e API-cd’s não promoveram ação citotóxica em células PC-12 nas concentrações testadas. Observou-se que três conjugados aumentaram a viabilidade das células PC-12, principalmente na concentração de 10μM. A API e API-cd’s não induziram citotoxicidade em cultura primária da medula espinhal nas concentrações testadas. A cultura primária da medula espinhal de ratos neonatos constitui diversidade morfológica de astrócitos, microglia e neurônios, além de agrupamentos de crescimento celular. As células da medula espinhal foram submetidas ao dano inflamatório por LPS a 5 μg/mL durante 12 horas. A API e API-cd 52 diminuíram a expressão de células IBA-1 e CD-68-positivas após o dano induzido por LPS. Duas API-cd’s reduziram de forma significativa os níveis de óxido nítrico. Duas API-cd’s reduziram de forma significativa o número de células S100β-positivas. CONCLUSÕES: A apigenina e os conjugados de apigenina parecem proteger as células da medula espinhal em modelo in vitro de neuroinflamação.pt_BR
dc.publisher.departmentInstituto de Ciências da Saúde - ICSpt_BR
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