Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model

PLoS One. 2014 May 12;9(5):e96750. doi: 10.1371/journal.pone.0096750. eCollection 2014.

Abstract

Aims: The aim of this study was to evaluate the effects of azilsartan (AZT) on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis.

Materials and methods: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1) nonligated, water; (2) ligated, water; (3) ligated, 1 mg/kg AZT; (4) ligated, 5 mg/kg AZT; and (5) ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA.

Results: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05) and IL-1β (p<0.05), increased levels of IL-10 (p<0.05), and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG.

Conclusions: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

MeSH terms

  • Animals
  • Benzimidazoles / therapeutic use*
  • Cathepsin K / blood*
  • Interleukin-10 / blood*
  • Interleukin-1beta / blood
  • Male
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Osteoprotegerin / blood*
  • Oxadiazoles / therapeutic use*
  • Periodontitis / blood*
  • Periodontitis / drug therapy*
  • Rats
  • Rats, Wistar
  • Receptor Activator of Nuclear Factor-kappa B / blood*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Benzimidazoles
  • Interleukin-1beta
  • Osteoprotegerin
  • Oxadiazoles
  • Receptor Activator of Nuclear Factor-kappa B
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Cathepsin K
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • azilsartan

Grants and funding

The authors have no support or funding to report.