title: Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver.
abstract: Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-κB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation.
  
  
  OBJECTIVE
  This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise.
  
  
  METHODS
  Twenty male Wistar rats were divided in four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout.
  
  
  RESULTS
  After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-κB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-κB pathway and the inflammatory response in the liver of exercised rats.
  
  
  CONCLUSIONS
  Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions.
authors: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil; Institute of Biomedicine (IBIOMED) and CIBERehd, University of León, Campus Universitario, 24071 León, Spain. Electronic address: romulo1604@hotmail.com.
authors: Rômulo Pillon
authors: RP
authors: Barcelos
authors: Instituto de Actividad Física y Salud, Universidad Autónoma de Chile, Chile.
authors: Guilherme
authors: G
authors: Bresciani
authors: Division of Clinical Translational Science, Georgia Prevention Institute, Department of Pediatrics, Georgia Regents University, USA.
authors: Paula
authors: P
authors: Rodriguez-Miguelez
authors: Institute of Biomedicine (IBIOMED) and CIBERehd, University of León, Campus Universitario, 24071 León, Spain.
authors: Maria José
authors: MJ
authors: Cuevas
authors: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors: Félix Alexandre Antunes
authors: FA
authors: Soares
authors: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
authors: Nilda Vargas
authors: NV
authors: Barbosa
authors: Institute of Biomedicine (IBIOMED) and CIBERehd, University of León, Campus Universitario, 24071 León, Spain.
authors: Javier
authors: J
authors: González-Gallego
mesh_terms: D000818:Animals; D004008:Diclofenac / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D004008:Diclofenac
keywords: Acute exercise; Diclofenac; Inflammation; Liver; NF-κB; TLR4