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dc.creatorMuniz, Igor Pereira Ribeiro-
dc.date.accessioned2023-07-10T10:38:34Z-
dc.date.available2023-07-10T10:38:34Z-
dc.date.issued2023-04-28-
dc.identifier.citationMUNIZ, Igor Pereira Ribeiro. Terapia fotodinâmica antimicrobiana (aPDT) com curcumina controla infecção intradérmica por Staphylococcus aureus resistente a meticilina em camundongos com diabetes tipo 1. 2023. Tese (doutorado em Ciências Fisiológicas) -Instituto Multidisciplinar em Saúde. Universidade Federal da Bahia, Vitória da Conquista, 2023.pt_BR
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/37318-
dc.description.abstractType 1 Diabetes Mellitus (T1DM) is a chronic non-communicable disease in which insulin is insufficiently produced due to the destruction of β cells in the pancreas. The changes generated by this condition increase the risk of infections for these individuals. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens causing infections in individuals with diabetes. In this work, we aimed to investigate the effects of the application of photodynamic therapy (PDT), using curcumin as a photosensitizer (PS), in the treatment of intradermal infection in mice with T1DM. C57bl/6 mice were weighed and, in a fasting state, their blood glucose was measured. DMT1 was induced by intraperitoneal injection of a single dose of streptozotocin (STZ) (180 mg/kg). Five days after STZ administration, the animals' blood glucose was measured to confirm the establishment of DMT1. Fifteen days after DMT1 induction, the animals were weighed and then infected intradermally in the left ear. For infection, the concentration of 1.5 x 107 CFU of the MRSA ATCC 4330 strain was quantified. Twenty-four hours after infection, the animals were separated in three groups. A solution containing 100 μg of curcumin was photoactivated ex vivo using LED light (450 nm) obtaining a fluence of 13.5 J/cm2 which consists in experimental group. After photoactivation, the solution was inoculated at the infection site. Control treatments consisted of the application of non-photoactivated curcumin or sterile saline. The animals were euthanized 24 h after the treatments and the left ear and left retromaxillary lymph node were surgically collected. The lymph node was macerated in saline for analysis of bacterial load, measurement of cytokines by ELISA, measurement of nitrites and nitrates, and cell counts. The ear was used to make slides that were stained by H&E or stained with anti-myeloperoxidase (MPO) antibodies by immunohistochemistry. Slides were photomicrographed and cell counts and tissue MPO expression analyzes were performed. The PDT group had a lower bacterial load in the lymph node when compared to controls (p-value <0.05). In addition to the lower bacterial load, the PDT group also had higher levels of nitrates and nitrites in the lymph node when compared to controls (p-value < 0.001). Cell recruitment to the infectious site on ear was similar between the PDT group compared with the control groups, however, the expression of MPO in the PDT group was less intense compared to the saline group (p-value < 0.001). When analyzing the production of cytokines, the PDT group showed lower production of IL-1, IL-12, and IL-10 (p-value <0.01; p-value <0.05; p-value < 0.05, respectively), when compared to the saline group. This study shows, for the first time, the therapeutic potential of PDT using curcumin in the treatment of an intradermal infection caused by S. aureus in mice with T1DM.pt_BR
dc.description.sponsorshipCAPESpt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahiapt_BR
dc.rightsAttribution-ShareAlike 3.0 Brazil*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/3.0/br/*
dc.subjectBiofotônicapt_BR
dc.subjectDiabetes Mellituspt_BR
dc.subjectMicrobiologiapt_BR
dc.subjectImunologiapt_BR
dc.subjectHistopatologiapt_BR
dc.subject.otherBiophotonicpt_BR
dc.subject.otherDiabetes Mellituspt_BR
dc.subject.otherMicrobiologypt_BR
dc.subject.otherImmunologypt_BR
dc.subject.otherHistopathologypt_BR
dc.titleTerapia fotodinâmica antimicrobiana (aPDT) com curcumina controla infecção intradérmica por Staphylococcus aureus resistente a meticilina em camundongos com Diabetes tipo 1pt_BR
dc.typeTesept_BR
dc.publisher.programPrograma Multicêntrico de Pós-Graduação em Ciências Fisiológicas (PMPGCF) pt_BR
dc.publisher.initialsUFBApt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPQ::CIENCIAS BIOLOGICASpt_BR
dc.contributor.advisor1Silva, Robson Amaro Augusto da-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2338026579762914pt_BR
dc.contributor.referee1Silva, Robson Amaro Augusto da-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/2338026579762914pt_BR
dc.contributor.referee2Gusmão, Amélia Cristina M. de Magalhães-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/6313221703674661pt_BR
dc.contributor.referee3Soares, Telma de Jesus-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/1755996803583447pt_BR
dc.contributor.referee4Rosa, Luciano Pereira-
dc.contributor.referee4Latteshttp://lattes.cnpq.br/8461453435410297pt_BR
dc.contributor.referee5Santos, Denisar Palmito dos-
dc.contributor.referee5Latteshttp://lattes.cnpq.br/0188625474025914pt_BR
dc.creator.IDhttps://orcid.org/0000-0003-1842-6432pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/7453565494403166pt_BR
dc.description.resumoO Diabetes Mellitus tipo 1 (DMT1) é uma doença crônica não transmissível na qual a insulina é produzida insuficientemente devido a destruição das células β no pâncreas. Mudanças geradas no funcionamento de sistemas, como o sistema imunológico, por esta condição aumenta o risco de infecções por estes indivíduos. Staphylococcus aureus resistente a meticilina (MRSA) é um dos principais patógenos causadores de infecções neste grupo. Este trabalho teve como objetivo investigar os efeitos da aplicação da terapia fotodinâmica (PDT), utilizando a curcumina como fotossensibilizante (FS), no tratamento de infecção intradérmica em camundongos com DMT1. Camundongos C57bl/6, foram pesados e, em jejum, tiveram a glicemia mensurada. O DMT1 foi induzido pela injeção intraperitoneal de uma dose única de estreptozotocina (STZ) (180 mg/kg). Cinco dias após a administração da STZ a glicemia dos animais foi mensurada para confirmar o estabelecimento do DMT1. Quinze dias após a indução do DMT1, os animais foram pesados e então infectados por MRSA (ATCC 43300) pela via intradérmica na orelha esquerda. Para a infecção, foi quantificada a concentração de 1,5 x 107 UFC da cepa MRSA ATCC 4330. Vinte e quatro horas após a infecção, os animais foram separados em 3 grupos. Uma solução contendo 100 μg de curcumina foi fotoativada ex vivo com o emprego de luz de LED (450 nm) obtendo uma fluência de 13.5 J/cm2. Após a fotoativação, a solução foi inoculada no sítio onde foi realizada a infecção nos animais, consistindo no grupo experimental. Os tratamentos controles consistiram na aplicação da curcumina não-fotoativado ou salina estéril. A eutanásia dos animais foi realizada 24 h após os tratamentos e a orelha esquerda e o linfonodo retromaxilar esquerdo foram cirurgicamente coletados. O linfonodo foi macerado em salina para análise da carga bacteriana, dosagem de citocinas por ELISA, dosagem de nitritos e nitratos e contagem de células. A orelha foi utilizada para a confecção de lâminas que foram coradas por H&E ou marcadas com anticorpos anti-mieloperoxidase (MPO) por imuno-histoquímica. As lâminas foram fotomicrografadas e contagens de células e análises de expressão de MPO no tecido foram realizadas. O grupo PDT apresentou menor carga bacteriana no linfonodo quando comparado aos controles (p-valor <0,05). Além da menor carga bacteriana, o grupo PDT também apresentou altos teores de nitratos e nitritos no linfonodo quando comparado aos controles (p-valor < 0,001). O recrutamento celular para a orelha apresentou-se similar entre o grupo PDT comparado aos controles, entretanto, a expressão da MPO no grupo PDT foi menos intensa comparada ao grupo salina (p-valor< 0,001). Quando analisada a produção de citocinas, o grupo PDT apresentou menores concentrações de IL-1, IL-12 e IL-10 (p-valor <0,01; p-valor <0,05; p-valor < 0,05, respectivamente), quando comparado ao grupo salina. Este estudo mostra, pela primeira vez, o potencial terapêutico da PDT usando curcumina no tratamento de uma infecção intradérmica causada por S. aureus em camundongos com DMT1.pt_BR
dc.publisher.departmentInstituto Multidisciplinar em Saúde (IMS)pt_BR
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