Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx

Detalhes bibliográficos
Autor(a) principal: Bonjorno, Reinaldo Carlos
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/19230
Resumo: Duchenne Muscular Dystrophy (DMD), affecting 1 in every 5,000 live births, affects the X chromosome, responsible for the synthesis of the dystrophin protein that maintains the stability of the cell membrane, making it resistant to mechanical forces. It causes ruptures, necrosis, and increased serum levels of cytoplasmic enzymes, which activate proteases, stimulating the degeneration of muscle fibers. The diagnosis is made through clinical examinations such as: muscle biopsy, Creatine Kinase (CK), and DNA measurement. Due to recurrent injuries, satellite cells are constantly activated to carry out the tissue repair process. In this way, these cells end up entering an exhaustion process, reducing the “pool” of quiescent cells, and affecting the regenerative process. Physical exercise is an important and low-cost therapy that has been explored in the rehabilitation of patients with DMD. Studies show that a lack of physical activity can determine changes in the functionality of the muscular, cardiac, and respiratory systems. Experimental studies with mdx mice have shown that low-intensity physical exercise increases the expression of CS, muscle mass, and strength and improves tissue cytoarchitecture. In parallel to therapies through physical exercise, DMD is also targeted by drugs. The most common of these is cortisol, a drug that is capable of significantly reducing the degenerative process of muscle fibers, but, on the other hand, causes side effects. Currently, melatonin has become the focus of research in the process of muscle regeneration after injury. Melatonin has several functions in the body, in addition to antioxidant and anti-inflammatory actions. Aiming at antioxidant and anti-inflammatory power, studies have shown that patients with DMD have increased expression of anti-inflammatory cytokines and these same authors have found a significant reduction in muscle necrosis markers. Exogenous administration of melatonin has been shown to increase the number of satellite cells and improve the strength and tissue morphology of normal skeletal muscles after physical exercise. Objective: Our objective was to analyze the morphofunctional and biochemical characteristics of dystrophic, skeletal, and cardiac muscles, after treatment with melatonin associated with low-intensity physical exercise. Results: The handgrip test showed that low-intensity aerobic exercise associated with melatonin induced a significant increase in grip strength in mdxTRM animals compared to mdxTR. In the morphological analysis of skeletal and cardiac muscles, it was possible to observe an improvement in the tissue morphology of the animals that were treated with melatonin in relation to the groups that did not receive the i.p. application. of melatonin. Regarding satellite cells, we can observe that the groups that completed the 21 training sessions presented greater PAX7 content, with the mdxTR group being the one that presented greater content compared to all other groups. For myogenin, the mdx and mdxM groups showed higher CS content in the fusion and differentiation phase, when compared to the trained groups. Using the Western Blot technique, we obtained promising results regarding the expression of the utrophin protein in the heart muscle, even without statistical significance.” The procedures imposed separately showed an increase in utrophin content when compared to the mdx group. The association of exercise and melatonin proved to be more efficient in morphology and in increasing the expression of utrophin. Conclusion: Both low-intensity aerobic exercise and melatonin improved the morphology of the psoas and cardiac muscles and also skeletal muscle function and when combined, these morphofunctional characteristics were even more expressive.
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spelling Bonjorno, Reinaldo CarlosCornachione, Anabelle Silvahttp://lattes.cnpq.br/0547232657871313http://lattes.cnpq.br/77369981684245782024-02-08T13:19:46Z2024-02-08T13:19:46Z2023-12-06BONJORNO, Reinaldo Carlos. Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx. 2023. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/19230.https://repositorio.ufscar.br/handle/ufscar/19230Duchenne Muscular Dystrophy (DMD), affecting 1 in every 5,000 live births, affects the X chromosome, responsible for the synthesis of the dystrophin protein that maintains the stability of the cell membrane, making it resistant to mechanical forces. It causes ruptures, necrosis, and increased serum levels of cytoplasmic enzymes, which activate proteases, stimulating the degeneration of muscle fibers. The diagnosis is made through clinical examinations such as: muscle biopsy, Creatine Kinase (CK), and DNA measurement. Due to recurrent injuries, satellite cells are constantly activated to carry out the tissue repair process. In this way, these cells end up entering an exhaustion process, reducing the “pool” of quiescent cells, and affecting the regenerative process. Physical exercise is an important and low-cost therapy that has been explored in the rehabilitation of patients with DMD. Studies show that a lack of physical activity can determine changes in the functionality of the muscular, cardiac, and respiratory systems. Experimental studies with mdx mice have shown that low-intensity physical exercise increases the expression of CS, muscle mass, and strength and improves tissue cytoarchitecture. In parallel to therapies through physical exercise, DMD is also targeted by drugs. The most common of these is cortisol, a drug that is capable of significantly reducing the degenerative process of muscle fibers, but, on the other hand, causes side effects. Currently, melatonin has become the focus of research in the process of muscle regeneration after injury. Melatonin has several functions in the body, in addition to antioxidant and anti-inflammatory actions. Aiming at antioxidant and anti-inflammatory power, studies have shown that patients with DMD have increased expression of anti-inflammatory cytokines and these same authors have found a significant reduction in muscle necrosis markers. Exogenous administration of melatonin has been shown to increase the number of satellite cells and improve the strength and tissue morphology of normal skeletal muscles after physical exercise. Objective: Our objective was to analyze the morphofunctional and biochemical characteristics of dystrophic, skeletal, and cardiac muscles, after treatment with melatonin associated with low-intensity physical exercise. Results: The handgrip test showed that low-intensity aerobic exercise associated with melatonin induced a significant increase in grip strength in mdxTRM animals compared to mdxTR. In the morphological analysis of skeletal and cardiac muscles, it was possible to observe an improvement in the tissue morphology of the animals that were treated with melatonin in relation to the groups that did not receive the i.p. application. of melatonin. Regarding satellite cells, we can observe that the groups that completed the 21 training sessions presented greater PAX7 content, with the mdxTR group being the one that presented greater content compared to all other groups. For myogenin, the mdx and mdxM groups showed higher CS content in the fusion and differentiation phase, when compared to the trained groups. Using the Western Blot technique, we obtained promising results regarding the expression of the utrophin protein in the heart muscle, even without statistical significance.” The procedures imposed separately showed an increase in utrophin content when compared to the mdx group. The association of exercise and melatonin proved to be more efficient in morphology and in increasing the expression of utrophin. Conclusion: Both low-intensity aerobic exercise and melatonin improved the morphology of the psoas and cardiac muscles and also skeletal muscle function and when combined, these morphofunctional characteristics were even more expressive.A Distrofia Muscular de Duchenne (DMD) afeta 1 a cada 5000 meninos nascidos vivos, atinge o cromossomo X, responsável pela síntese da proteína distrofina que mantem a estabilidade da membrana celular. Sua ausência causa rupturas, necroses e aumento dos níveis séricos de enzimas citoplasmáticas o que ativa as proteases estimulando a degeneração das fibras musculares. O diagnóstico é feito através de exames, tais como: biópsia muscular, dosagem de Creatina Quinase (CK) e DNA. Devido as lesões recorrentes, células satélites (CS) são constantemente ativadas. Dessa maneira as CS entram em exaustão, reduzindo o “pool” de células quiescentes, afetando o processo regenerativo. O exercício físico mostra ser eficiente na terapêutica de pacientes com DMD. Estudos com animais mdx mostraram que o exercício físico de baixa intensidade aumentou a expressão de CS, da massa muscular, de força e melhora na citoarquitetura tecidual. Em paralelo as terapias com exercício, a DMD também é alvo de terapias farmacológicas. A droga mais comum utilizada é o cortisol, pois é capaz de reduzir significativamente processo degenerativo das fibras musculares, porém apresenta muitos efeitos colaterais indesejáveis. Atualmente, a melatonina vem sendo foco de muitas investigações científicas, pois apresenta diversas funcionalidades no organismo, além de ação antioxidante e anti-inflamatória. Visando o poder antioxidante e anti-inflamatório, estudos mostraram que pacientes com DMD aumentaram a expressão de citocinas anti-inflamatórias e redução significativa de marcadores de necrose muscular. O uso de melatonina mostrou aumentar o número de células satélites, melhorar a força e a morfologia do músculo esquelético normal, após exercício. Objetivo: Analisar as características morfofuncionais e bioquímicas de músculos distróficos, esquelético e cardíaco, após tratamento com melatonina associada ao exercício. Resultados: O teste de preensão palmar mostrou que o exercício associado a melatonina induziu aumento de força de preensão significativa nos animais mdxTRM em relação aos mdxTR. Na análise morfológica dos músculos esqueléticos e cardíacos, mostrou melhora na morfologia tecidual dos animais tratados com melatonina em relação aos que não receberam. Com relação as células satélites o grupo mdxTR apresentou maior número de CS ativas em proliferação. Para CS em diferenciação os grupos mdx e mdxM, apresentaram maior número de CS, quando comparados aos grupos treinados. Na técnica de Western Blot mostrou aumento na expressão de utrofina no músculo cardíaco dos animais do grupo mdxTRM. Conclusão: Tanto exercício quanto a melatonina melhoraram a morfologia dos músculos psoas, cardíaco e função muscular esquelética, quando associados essas características morfofuncionais foram ainda mais expressivas.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)131521/2021-7porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessDistrofia muscular de DuchenneCamundongos mdxMelatoninaExercício aeróbico de baixa intensidadeUtrofinaCélulas satélitesMúsculo esqueléticoMúsculo cardíacoDuchenne muscular dystrophymdx miceMelatoninLow-intensity aerobic exerciseUtrophinSatellite cellsSkeletal muscleCardiac muscleCIENCIAS BIOLOGICAS::FISIOLOGIAEfeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdxEffects of low-intensity aerobic exercise and melatonin on skeletal and cardiac muscles of mdx miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissertação_biblioteca_Reinaldo Carlos Bonjorno.pdfDissertação_biblioteca_Reinaldo Carlos Bonjorno.pdfDissertação Finalapplication/pdf6264790https://repositorio.ufscar.br/bitstream/ufscar/19230/4/Disserta%c3%a7%c3%a3o_biblioteca_Reinaldo%20Carlos%20Bonjorno.pdf24d78a49c40f275750845ac7cf683361MD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8810https://repositorio.ufscar.br/bitstream/ufscar/19230/5/license_rdff337d95da1fce0a22c77480e5e9a7aecMD55TEXTDissertação_biblioteca_Reinaldo Carlos Bonjorno.pdf.txtDissertação_biblioteca_Reinaldo Carlos Bonjorno.pdf.txtExtracted texttext/plain149206https://repositorio.ufscar.br/bitstream/ufscar/19230/6/Disserta%c3%a7%c3%a3o_biblioteca_Reinaldo%20Carlos%20Bonjorno.pdf.txte54f680febd4a51237b211ca32e086c7MD56ufscar/192302024-05-14 17:30:11.462oai:repositorio.ufscar.br:ufscar/19230Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222024-05-14T17:30:11Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
dc.title.alternative.eng.fl_str_mv Effects of low-intensity aerobic exercise and melatonin on skeletal and cardiac muscles of mdx mice
title Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
spellingShingle Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
Bonjorno, Reinaldo Carlos
Distrofia muscular de Duchenne
Camundongos mdx
Melatonina
Exercício aeróbico de baixa intensidade
Utrofina
Células satélites
Músculo esquelético
Músculo cardíaco
Duchenne muscular dystrophy
mdx mice
Melatonin
Low-intensity aerobic exercise
Utrophin
Satellite cells
Skeletal muscle
Cardiac muscle
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
title_full Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
title_fullStr Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
title_full_unstemmed Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
title_sort Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx
author Bonjorno, Reinaldo Carlos
author_facet Bonjorno, Reinaldo Carlos
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/7736998168424578
dc.contributor.author.fl_str_mv Bonjorno, Reinaldo Carlos
dc.contributor.advisor1.fl_str_mv Cornachione, Anabelle Silva
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0547232657871313
contributor_str_mv Cornachione, Anabelle Silva
dc.subject.por.fl_str_mv Distrofia muscular de Duchenne
Camundongos mdx
Melatonina
Exercício aeróbico de baixa intensidade
Utrofina
Células satélites
Músculo esquelético
Músculo cardíaco
topic Distrofia muscular de Duchenne
Camundongos mdx
Melatonina
Exercício aeróbico de baixa intensidade
Utrofina
Células satélites
Músculo esquelético
Músculo cardíaco
Duchenne muscular dystrophy
mdx mice
Melatonin
Low-intensity aerobic exercise
Utrophin
Satellite cells
Skeletal muscle
Cardiac muscle
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Duchenne muscular dystrophy
mdx mice
Melatonin
Low-intensity aerobic exercise
Utrophin
Satellite cells
Skeletal muscle
Cardiac muscle
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description Duchenne Muscular Dystrophy (DMD), affecting 1 in every 5,000 live births, affects the X chromosome, responsible for the synthesis of the dystrophin protein that maintains the stability of the cell membrane, making it resistant to mechanical forces. It causes ruptures, necrosis, and increased serum levels of cytoplasmic enzymes, which activate proteases, stimulating the degeneration of muscle fibers. The diagnosis is made through clinical examinations such as: muscle biopsy, Creatine Kinase (CK), and DNA measurement. Due to recurrent injuries, satellite cells are constantly activated to carry out the tissue repair process. In this way, these cells end up entering an exhaustion process, reducing the “pool” of quiescent cells, and affecting the regenerative process. Physical exercise is an important and low-cost therapy that has been explored in the rehabilitation of patients with DMD. Studies show that a lack of physical activity can determine changes in the functionality of the muscular, cardiac, and respiratory systems. Experimental studies with mdx mice have shown that low-intensity physical exercise increases the expression of CS, muscle mass, and strength and improves tissue cytoarchitecture. In parallel to therapies through physical exercise, DMD is also targeted by drugs. The most common of these is cortisol, a drug that is capable of significantly reducing the degenerative process of muscle fibers, but, on the other hand, causes side effects. Currently, melatonin has become the focus of research in the process of muscle regeneration after injury. Melatonin has several functions in the body, in addition to antioxidant and anti-inflammatory actions. Aiming at antioxidant and anti-inflammatory power, studies have shown that patients with DMD have increased expression of anti-inflammatory cytokines and these same authors have found a significant reduction in muscle necrosis markers. Exogenous administration of melatonin has been shown to increase the number of satellite cells and improve the strength and tissue morphology of normal skeletal muscles after physical exercise. Objective: Our objective was to analyze the morphofunctional and biochemical characteristics of dystrophic, skeletal, and cardiac muscles, after treatment with melatonin associated with low-intensity physical exercise. Results: The handgrip test showed that low-intensity aerobic exercise associated with melatonin induced a significant increase in grip strength in mdxTRM animals compared to mdxTR. In the morphological analysis of skeletal and cardiac muscles, it was possible to observe an improvement in the tissue morphology of the animals that were treated with melatonin in relation to the groups that did not receive the i.p. application. of melatonin. Regarding satellite cells, we can observe that the groups that completed the 21 training sessions presented greater PAX7 content, with the mdxTR group being the one that presented greater content compared to all other groups. For myogenin, the mdx and mdxM groups showed higher CS content in the fusion and differentiation phase, when compared to the trained groups. Using the Western Blot technique, we obtained promising results regarding the expression of the utrophin protein in the heart muscle, even without statistical significance.” The procedures imposed separately showed an increase in utrophin content when compared to the mdx group. The association of exercise and melatonin proved to be more efficient in morphology and in increasing the expression of utrophin. Conclusion: Both low-intensity aerobic exercise and melatonin improved the morphology of the psoas and cardiac muscles and also skeletal muscle function and when combined, these morphofunctional characteristics were even more expressive.
publishDate 2023
dc.date.issued.fl_str_mv 2023-12-06
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dc.identifier.citation.fl_str_mv BONJORNO, Reinaldo Carlos. Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx. 2023. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/19230.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/19230
identifier_str_mv BONJORNO, Reinaldo Carlos. Efeitos do exercício aeróbio de baixa intensidade e da melatonina nos músculos esquelético e cardíaco de camundongos mdx. 2023. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/ufscar/19230.
url https://repositorio.ufscar.br/handle/ufscar/19230
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dc.publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.publisher.program.fl_str_mv Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCF
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