In vivo exposure to hydroquinone during the early phase of collagen-induced arthritis aggravates the disease

Toxicology. 2018 Sep 1:408:22-30. doi: 10.1016/j.tox.2018.06.010. Epub 2018 Jun 21.

Abstract

Robust correlation between the severity of rheumatoid arthritis (RA) and cigarette smoking has been clinically demonstrated. Nevertheless, cigarette compounds responsible for this toxic effect and their mechanisms have not been described. Considering that hydroquinone (HQ) is an abundant, pro-oxidative compound of the matter particle phase of cigarette smoke, we investigated whether HQ exposure during the initial phase of collagen-induced arthritis (CIA) could aggravate the disease. For this purpose, male Wistar rats were exposed to aerosolized HQ (25 ppm), saline or 5% ethanol solution (HQ vehicle) for 1 h per day during 14 days. CIA was induced through s.c. injection of bovine collagen Type II (0.4 mg/100 μL) at days seven and 14 of exposure. Clinical signs of disease and the cell profile and chemical mediators in the synovial fluid and membrane were analysed at day 35 after the beginning of exposure. HQ exposure aggravated CIA-related paw edema and increased the cell infiltrate and interleukin-6 (IL-6) levels in the synovial fluid, promoted intense tissue collagen deposition and enhanced synoviocyte proliferation and higher frequency of aryl hydrocarbon receptor (AhR+) and interleukin (IL-17+) neutrophils in the synovial membrane. in vitro data also highlighted that neutrophils expressed increased levels of AhR, IL-17 and reactive oxygen species (ROS) generation. However, only AhR expression and ROS generation were blocked by in vitro treatment with AhR antagonist. Therefore, we conclude that in vivo HQ exposure at the early phase of AR onset worsens RA, leading to high frequency of AhR/IL-17+ neutrophils into the joint.

Keywords: AhR; Cigarette smoke; Environmental toxicology; IL-17; Neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Animals
  • Arthritis, Experimental / chemically induced*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Collagen Type II*
  • Hydroquinones / administration & dosage
  • Hydroquinones / toxicity*
  • Inflammation Mediators / metabolism
  • Inhalation Exposure
  • Interleukin-17 / metabolism
  • Male
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / metabolism
  • Synovial Fluid / metabolism
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism
  • Synoviocytes / pathology
  • Time Factors

Substances

  • Aerosols
  • Ahr protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • Collagen Type II
  • Hydroquinones
  • Il17a protein, rat
  • Inflammation Mediators
  • Interleukin-17
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • hydroquinone