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dc.creatorMalheiro, Lara Fabiana Luz-
dc.date.accessioned2024-03-05T14:46:13Z-
dc.date.available2024-03-05T14:46:13Z-
dc.date.issued2024-02-21-
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/39149-
dc.description.abstractCisplatin (CP) is a chemotherapy agent widely used to treat various types of solid tumors. However, its lack of selectivity affects healthy cells, causing several cytotoxic effects, including hepatotoxicity. Although the underlying mechanisms of hepatotoxicity are not fully understood, evidence suggests a significant involvement of the inflammatory process in the exacerbation and progression of tissue damage. Recently, some studies have reported the hepatoprotective effects mediated by regular aerobic physical exercise. However, it is still unclear which intensity is most effective in enhancing these protective effects, especially in acute liver injuries. Therefore, this study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of light (LIT) and moderate (MIT) intensities on inflammatory markers in Wistar rats with CP-induced hepatotoxicity. For this purpose, 35 Wistar female rats were divided into five groups (n=7 in each group): control and sedentary (C+S); treated with CP and sedentary (CP+S); treated with CP and subjected to LIT (CP+LIT); treated with CP and subjected to MIT (CP+MIT); and treated with CP and subjected to HIIT (CP+HIIT). The training protocols consisted of treadmill running, 5 days a week, for 8 weeks before the CP treatment. At the end of the 8-week training period, the rats received a single injection of CP (5 mg/kg i.p) or saline, and 7 days after the injection, they were euthanized. Liver samples were collected to evaluate the expression of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α, IL-1β, IL-6, IL-8, and IL-10, the number of ED-1 positive cells, and M1 (iNOS) and M2 (arginase 1) macrophages markers in the hepatic tissue. Our results show that CP treatment promoted na increase in all pro-inflammatory markers, including TLR4/ NF-κB, pro-inflammatory cytokines, immunostaining of ED-1 positive cells, and expressions of M1 macrophage marker compared to the control group. However, HIIT was the most effective exercise protocol in reducing the increase in all these markes compared to LIT and MIT protocols. Additionally, preconditioning with HIIT potentiated the anti-inflammatory cytokine IL-10 and the M2 macrophage marker expressions, while reducing the expression of the M1 macrophage marker in liver. Thus, the present study suggests that physical preconditioning with HIIT was more effective in promoting hepatoprotective effects than LIT and MIT preconditioning protocols, regulating important inflammatory markers through modulation of the TLR4/NF-κB signaling pathway.pt_BR
dc.description.sponsorshipCNPqpt_BR
dc.description.sponsorshipFapesbpt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahia/Campus Anísio Teixeirapt_BR
dc.subjectHepatotoxicidade.pt_BR
dc.subjectCisplatinapt_BR
dc.subjectExercício Fisicopt_BR
dc.subjectHIITpt_BR
dc.subjectInflamaçãopt_BR
dc.subject.otherHepatotoxicitypt_BR
dc.subject.otherCisplatinpt_BR
dc.subject.otherPhysical exercisept_BR
dc.subject.otherHIITpt_BR
dc.subject.otherInflammationpt_BR
dc.titleTreinamento intervalado de alta intensidade atenua a inflamação hepática através da via de sinalização TLR4/NF-kB em ratas com hepatotoxicidade induzida por cisplatinapt_BR
dc.typeDissertaçãopt_BR
dc.publisher.programPrograma Multicêntrico de Pós-Graduação em Ciências Fisiológicas (PMPGCF) pt_BR
dc.publisher.initialsUFBA/CATpt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPq Ciências Biológicaspt_BR
dc.contributor.advisor1Amaral, Liliany Souza de Brito-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/7005117412401272pt_BR
dc.contributor.referee1Amaral, Liliany Souza de Brito-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/7005117412401272pt_BR
dc.contributor.referee2Gusmão, Amélia Cristina Mendes de Magalhães-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/6313221703674661pt_BR
dc.contributor.referee3Coqueiro, Raildo da Silva-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/1515934360117525pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/8252073883331582pt_BR
dc.description.resumoA cisplatina (CP) é um quimioterápico amplamente utilizado para o tratamento de vários tipos de tumores sólidos, contudo a falta de seletividade afeta células saudáveis, provocando diversos efeitos citotóxicos, incluindo a hepatotoxicidade. Embora os mecanismos envolvidos na hepatotoxicidade não estejam totalmente esclarecidos, evidências apontam para uma importante participação do processo inflamatório no agravamento e progressão dos danos teciduais. Recentemente, alguns estudos têm reportado os efeitos hepatoprotetores da prática regular de exercícios físicos aeróbicos, contudo ainda não está clara a influência da manipulação de suas variáveis sobre tal hepatoproteção, especialmente em lesões hepáticas agudas. Assim, este estudo tem como objetivo comparar os efeitos entre o pré-condicionamento com o treinamento intervalado de alta intensidade (HIIT) e treinamentos tradicionais contínuos de leve (LIT) e moderada (MIT) intensidades sobre marcadores inflamatórios em ratas wistar com hepatotoxicidade induzida por CP. Para tanto, 35 ratas wistar foram divididas em cinco grupos (n=7 em cada grupo): controle e sedentários (C+S); tratados com CP e sedentário (CP+S); tratados com CP e submetidos ao LIT (CP+LIT); tratados com CP e submetidos ao MIT (CP+MIT) e tratados com CP e submetidos ao HIIT (CP+HIIT). Os protocolos de treinamentos consistiram de corrida em esteira motorizada, 5 dias por semana, por 8 semanas, antes do tratamento com CP. Ao final das 8 semanas de treinamento, as ratas receberam uma única injeção de CP (5 mg/kg i.p) ou solução salina, e 7 dias depois da injeção foram eutanasiadas. Amostras do fígado foram coletadas para avaliar a expressão do fator de transcrição nuclear kappa B (NF-κB), do receptor toll like 4 (TLR4), fator de necrose tumoral alfa (TNF-α), interleucina (IL)-1α, IL-1β, IL-6, IL-8 e IL-10, o número de células ED-1 positivas e marcadores de macrófagos M1 (iNOS) e M2 (arginase 1) no tecido hepático. Os nossos resultados mostram que o tratamento com a CP promoveu aumento de todos os marcadores pró-inflamatórios, incluindo TLR4/NF-κB, citocinas pró-inflamatórias, imunomarcação de células ED-1 positivas e expressão do marcador de macrófago do tipo M1 em relação ao grupo controle. No entanto, o HIIT foi o protocolo de exercício mais eficaz em reduzir o aumento de todos esses marcadores quando comparado aos protocolos LIT e MIT. Adicionalmente, o pré-condicionamento com o HIIT potencializou as expressões da citocina anti-inflamatória IL-10 e do marcador de macrófagos do tipo M2, ao passo em que reduziu a expressão do marcador de macrófagos do tipo M1 no tecido hepático. Desse modo, o presente estudo sugere que o pré-condicionamento físico com o HIIT foi mais eficaz em promover efeitos hepatoprotetores do que os protocolos de pré-condicionamentos com LIT e MIT, regulando importantes marcadores inflamatórios através da modulação da via de sinalização TLR4/NF-κB no tecido hepático de ratas tratadas com CP.pt_BR
dc.publisher.departmentInstituto Multidisciplinar em Saúde (IMS)pt_BR
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