Rômulo Pillon Barcelos1, Guilherme Bresciani2, Paula Rodriguez-Miguelez3, Maria José Cuevas4, Félix Alexandre Antunes Soares5, Nilda Vargas Barbosa5, Javier González-Gallego4. 1. 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. 2. Instituto de Actividad Física y Salud, Universidad Autónoma de Chile, Chile. 3. Division of Clinical Translational Science, Georgia Prevention Institute, Department of Pediatrics, Georgia Regents University, USA. 4. Institute of Biomedicine (IBIOMED) and CIBERehd, University of León, Campus Universitario, 24071 León, Spain. 5. Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.
Abstract
UNLABELLED: 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. AIMS: This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions.
UNLABELLED: 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. AIMS: This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions.