Olmesartan decreases IL-1β and TNF-α levels; downregulates MMP-2, MMP-9, COX-2, and RANKL; and upregulates OPG in experimental periodontitis

Naunyn Schmiedebergs Arch Pharmacol. 2013 Oct;386(10):875-84. doi: 10.1007/s00210-013-0886-8. Epub 2013 Jun 19.


The objective of this study is to investigate the participation of inflammatory and oxidative stress mediators and the effects on the expression of matrix metalloproteinase (MMP)-2, MMP-9, and receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) pathway in the response to treatment with olmesartan, an angiotensin II type 1 receptor blocker. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1) non-ligature with water, (2) ligature with water, (3) ligature with 1 mg/kg olmesartan, (4) ligature with 6 mg/kg olmesartan, and (5) ligature with 10 mg/kg olmesartan. All groups were treated with olmesartan or the vehicle by gavage daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by histopathology and immunohistochemistry to determine the expression of cyclooxygenase-2 (COX-2), MMP-2, MMP-9, and members of the RANKL/RANK/OPG pathway and by ELISA and spectroscopic assay to determine the levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malonaldehyde (MDA), and glutathione. The concentrations of MPO and MDA were reduced in the group that received 6 mg/kg olmesartan (p < 0.05). In addition, the group that was treated with 6 mg/kg olmesartan showed a decreased level of IL-1β (p < 0.05), and all doses of olmesartan resulted in decreased levels of TNF-α. Furthermore, treatment with 6 mg/kg olmesartan led to downregulation of the expression of COX-2, MMP-2, MMP-9, RANKL, and RANK and to upregulation of the expression of OPG. These findings suggest that 6 mg/kg olmesartan reduces the inflammatory process and bone loss by downregulating MMPs and RANKL in osteoblasts and by upregulating OPG.

MeSH terms

  • Alveolar Bone Loss / drug therapy
  • Alveolar Bone Loss / metabolism*
  • Alveolar Bone Loss / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Cyclooxygenase 2 / metabolism
  • Gingiva / drug effects
  • Gingiva / metabolism
  • Gingiva / pathology
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Interleukin-1beta / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Osteoprotegerin / metabolism
  • Periodontitis / drug therapy
  • Periodontitis / metabolism*
  • Periodontitis / pathology
  • Peroxidase / metabolism
  • RANK Ligand / metabolism
  • Rats
  • Rats, Wistar
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Imidazoles
  • Interleukin-1beta
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tetrazoles
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • olmesartan
  • Peroxidase
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat