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Efeito modulador in vitro de um complexo de inclusão resveratrol-metil-β-ciclodextrina sobre a inflamação e o estresse oxidativo induzidos pela hemina na doença falciforme.
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| dc.creator | Oliveira, Yasmin da Silva | |
| dc.date.accessioned | 2025-10-03T17:57:02Z | |
| dc.date.available | 2027-06-17 | |
| dc.date.available | 2025-10-03T17:57:02Z | |
| dc.date.issued | 2025-06-17 | |
| dc.identifier.citation | OLIVEIRA, Yasmin da Silva. Efeito modulador in vitro de um complexo de inclusão resveratrol-metil-β-ciclodextrina sobre a inflamação e o estresse oxidativo induzido pela hemina na doença falciforme. Orientador: Vitor Fortuna; Coorientador: Roberto José Meyer Nascimento. 2025. 75 f. Dissertação (Mestrado em Imunologia) - Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador (BA), 2025. | pt_BR |
| dc.identifier.uri | https://repositorio.ufba.br/handle/ri/43133 | |
| dc.description.abstract | Introduction: Sickle cell disease (SCD) is a hemoglobinopathy characterized by the formation of hemoglobin S (HbS). When deoxygenated, HbS triggers polymerization, aggregation, and hemolysis, releasing products such as heme, which in turn initiate inflammatory processes and oxidative stress. Resveratrol (RES) is a polyphenol described as having anti-inflammatory and antioxidant properties in vitro, but with limited bioavailability. Cyclodextrins (CD) enable the formation of inclusion complexes with hydrophobic molecules like resveratrol, enhancing its bioavailability. Objective: To investigate the effect of a resveratrol–methyl-β-cyclodextrin (RES-MBCD) inclusion complex on hemin-induced oxidative and pro-inflammatory stress in THP-1 cells and peripheral blood mononuclear cells (PBMC) from SCD patients. Materials and Methods: Cells were pre-treated with RES-MBCD (5, 15, and 25 µM) prior to induction of stress with hemin (30 or 70 µM). RES-MBCD cytotoxicity, DPPH radical scavenging activity, reactive oxygen species (ROS) production, lipid peroxide levels, and the quantification of pro-inflammatory cytokines (TNF-α and IL-6) were assessed. Results: RES-MBCD did not exhibit significant cytotoxicity on THP-1 cells at 24 hours and showed lower cytotoxicity compared to free RES at 72 hours (p < 0.0001), along with greater DPPH radical scavenging capacity (p < 0,05). RES-MBCD reduced ROS production (p < 0.01) and TNF-α quantification (p < 0.05) induced by hemin in THP-1 cells. However, it increased TNF-α (p < 0.05) and IL-6 (p < 0,05) quantification in PBMC from SCD patients. Conclusion: These findings suggest that RES-MBCD exhibits remarkable antioxidant and immunomodulatory effects against hemin-induced stress, with lower cytotoxicity compared to free RES, highlighting the potential of resveratrol as a bioactive compound of therapeutic interest in SCD. | pt_BR |
| dc.description.sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) | pt_BR |
| dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) | pt_BR |
| dc.language | por | pt_BR |
| dc.publisher | Universidade Federal da Bahia | pt_BR |
| dc.rights | Acesso Restrito/Embargado | pt_BR |
| dc.subject | Doença falciforme | pt_BR |
| dc.subject | Anemia Falciforme | pt_BR |
| dc.subject | Heme | pt_BR |
| dc.subject | Inflamação | pt_BR |
| dc.subject | Estresse oxidativo | pt_BR |
| dc.subject | Resveratrol | pt_BR |
| dc.subject | Ciclodextrinas | pt_BR |
| dc.subject.other | Sickle cell disease | pt_BR |
| dc.subject.other | Anemia, Sickle Cell | pt_BR |
| dc.subject.other | Heme | pt_BR |
| dc.subject.other | Inflammation | pt_BR |
| dc.subject.other | Oxidative stress | pt_BR |
| dc.subject.other | Resveratrol | pt_BR |
| dc.subject.other | Cyclodextrins | pt_BR |
| dc.title | Efeito modulador in vitro de um complexo de inclusão resveratrol-metil-β-ciclodextrina sobre a inflamação e o estresse oxidativo induzidos pela hemina na doença falciforme. | pt_BR |
| dc.title.alternative | In vitro modulatory effect of a resveratrol-methyl-β-cyclodextrin inclusion complex on hemin-induced inflammation and oxidative stress in sickle cell disease. | pt_BR |
| dc.type | Dissertação | pt_BR |
| dc.publisher.program | Programa de Pós-Graduação em Imunologia - (PPGIM) | pt_BR |
| dc.publisher.initials | UFBA | pt_BR |
| dc.publisher.country | Brasil | pt_BR |
| dc.subject.cnpq | CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA | pt_BR |
| dc.contributor.advisor1 | Fortuna, Vitor Antonio | |
| dc.contributor.advisor1ID | https://orcid.org/0000-0001-7281-3287 | pt_BR |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/3535550424970530 | pt_BR |
| dc.contributor.advisor-co1 | Nascimento, Roberto José Meyer | |
| dc.contributor.advisor-co1ID | https://orcid.org/0000-0002-4727-4805 | pt_BR |
| dc.contributor.advisor-co1Lattes | http://lattes.cnpq.br/9574426480028427 | pt_BR |
| dc.contributor.referee1 | Fortuna, Vitor Antonio | |
| dc.contributor.referee1ID | https://orcid.org/0000-0001-7281-3287 | pt_BR |
| dc.contributor.referee1Lattes | http://lattes.cnpq.br/3535550424970530 | pt_BR |
| dc.contributor.referee2 | Barbosa, Cynara Gomes | |
| dc.contributor.referee2ID | https://orcid.org/0000-0003-2856-3756 | pt_BR |
| dc.contributor.referee2Lattes | http://lattes.cnpq.br/1464729909848094 | pt_BR |
| dc.contributor.referee3 | Silva, Victor Diógenes Amaral da | |
| dc.contributor.referee3ID | https://orcid.org/0000-0001-8032-9663 | pt_BR |
| dc.contributor.referee3Lattes | http://lattes.cnpq.br/6166491745017786 | pt_BR |
| dc.creator.ID | https://orcid.org/0009-0003-7415-5128 | pt_BR |
| dc.creator.Lattes | http://lattes.cnpq.br/2606151750393033 | pt_BR |
| dc.description.resumo | Introdução: A doença falciforme (DF) é uma hemoglobinopatia caracterizada pela formação de hemoglobina S (HbS). Quando desoxigenada, a HbS desencadeia polimerização, agregação e hemólise, liberando produtos como o heme, que provoca processos inflamatórios e estresse oxidativo. O resveratrol (RES) é um polifenol descrito como anti-inflamatório e antioxidante in vitro, mas com biodisponibilidade limitada. Ciclodextrinas (CD) permitem a formação de complexos de inclusão com moléculas hidrofóbicas como o resveratrol, melhorando sua biodisponibilidade. Objetivo: Investigar o efeito do complexo de inclusão resveratrol-metil-β-ciclodextrina (RES-MBCD) no estresse oxidativo e pró-inflamatório induzido por hemina em células THP-1 e células mononucleares do sangue periférico (PBMC) de pacientes com doença falciforme. Materiais e métodos: As células foram pré-tratadas com RES MBCD (5, 15 e 25 µM) antes da indução do estresse com hemina (30 ou 70 µM). A citotoxicidade do RES-MBCD, inibição do radical DPPH, produção de espécies reativas de oxigênio, peróxidos lipídicos e quantificação de citocinas pró-inflamatórias (TNF-α e IL-6) foram avaliadas. Resultados: O RES-MBCD não demonstrou citotoxicidade significativa sobre células THP-1 em 24h e menor citotoxicidade em células THP-1 em comparação ao resveratrol livre em 72h (p < 0,0001), além de maior capacidade de inibição do radical DPPH (p < 0,05). RES-MBCD diminuiu a produção de ERO (p < 0,01) e a quantificação de TNF-α (p < 0,05) induzida pela hemina em células THP-1. Entretanto, aumentou a quantificação de TNF-α (p < 0,05) e IL-6 (p < 0,05) em PBMC de pacientes com DF. Conclusão: Esses dados sugerem que o RES MBCD tem notável efeito antioxidante e imunomodulador frente ao estresse causado pela hemina, com menor citotoxicidade em relação ao RES livre, reforçando o potencial do resveratrol como composto bioativo de interesse terapêutico na DF. | pt_BR |
| dc.publisher.department | Instituto de Ciências da Saúde - ICS | pt_BR |
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| dc.type.degree | Mestrado Acadêmico | pt_BR |
