The Effects of Resveratrol on Inflammation and Oxidative Stress in a Rat Model of Chronic Obstructive Pulmonary Disease

Molecules. 2017 Sep 12;22(9):1529. doi: 10.3390/molecules22091529.

Abstract

Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Resveratrol (trans-3,5,4'-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties. The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α). Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group. The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS). The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured. The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis. After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen. Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression. Resveratrol treatment decreased serum levels of IL-6 and IL-8. Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response. The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways. Thus resveratrol might be a therapeutic modality in COPD.

Keywords: COPD; PGC-1α; SIRT1; cigarette smoke; lipopolysaccharide; oxidative stress; resveratrol.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Interleukin-8 / blood
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / adverse effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Rats
  • Resveratrol
  • Signal Transduction / drug effects
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Stilbenes / pharmacology*
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Stilbenes
  • Malondialdehyde
  • Superoxide Dismutase
  • SIRT1 protein, human
  • Sirtuin 1
  • Resveratrol