The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin

Toxicol Appl Pharmacol. 2017 Dec 1;336:40-48. doi: 10.1016/j.taap.2017.10.001. Epub 2017 Oct 4.

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced endogenous antioxidant defense, shown by a reduced total antioxidant capacity and lowered glutathione and uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory cytokines IL-8 and TNFα. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of bleomycin-triggered BEAS-2B cells, shows that quercetin boosts the antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of quercetin to restore the disturbed redox balance and reduce inflammation.

Keywords: Antioxidants; Idiopathic pulmonary fibrosis (IPF); Inflammation; Interstitial lung diseases (ILD); Oxidative stress; Quercetin.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Bleomycin / toxicity
  • Case-Control Studies
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology
  • Inflammation Mediators / metabolism
  • Interleukin-8 / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Quercetin / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • CXCL8 protein, human
  • Inflammation Mediators
  • Interleukin-8
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Bleomycin
  • Quercetin