title: Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.
abstract: Nonsteroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the toll-like receptor-nuclear factor kappa B (TLR-NF-κB) pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into 4 groups: control-saline, control-diclofenac, exercise-saline, and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout. The inflammatory status was evaluated through mRNA levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNF-α), and protein content of COX-2, IL-6, and TNF-α in vastus lateralis muscle. Data obtained showed that a single bout of eccentric exercise significantly increased COX-2 gene expression. Similarly, mRNA expression and protein content of other inflammation-related genes also increased after the acute exercise. However, these effects were attenuated in the exercise + diclofenac group. TLR4, myeloid differentiation primary response gene 88 (MyD88), and p65 were also upregulated after the acute eccentric bout and the effect was blunted by the anti-inflammatory drug. These findings suggest that pretreatment with diclofenac may represent an effective tool to ameliorate the pro-inflammatory status induced by acute exercise in rat skeletal muscle possibly through an attenuation of the TLR4-NF-κB signaling pathway.
authors.affiliation: a Programa de Pós-graduação em Bioexperimentação, Universidade de Passo Fundo, RS, 99052-900, Brazil.|c Institute of Biomedicine, University of León, Campus Universitario, 24071 León, Spain.|d Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900 Brazil.
authors.forename: Rômulo Pillon
authors.initials: RP
authors.lastname: Barcelos
authors.affiliation: b Grupo de Investigación en Rendimiento Físico y Salud Escuela de Educación Física, Pontificia Universidad Católica de Valparaiso, Valparaiso, 2530388 Chile.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Bresciani
authors.affiliation: c Institute of Biomedicine, University of León, Campus Universitario, 24071 León, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Cuevas
authors.affiliation: c Institute of Biomedicine, University of León, Campus Universitario, 24071 León, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Martínez-Flórez
authors.affiliation: e Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Félix Alexandre Antunes
authors.initials: FAA
authors.lastname: Soares
authors.affiliation: c Institute of Biomedicine, University of León, Campus Universitario, 24071 León, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: González-Gallego
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D004008:Diclofenac; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: AINS; COX; NF-κB; NSAIDs; eccentric exercise; exercice pliométrique; inflammation; muscle squelettique; skeletal muscle