Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 10, pp 875–884 | Cite as

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

  • Aurigena Antunes Araújo
  • Graziene Lopes de Souza
  • Tatiana Oliveira Souza
  • Gerly Anne de Castro Brito
  • Karoline Sabóia Aragão
  • Caroline Addison Xavier de Medeiros
  • Yriu Lourenço
  • Maria do Socorro Costa Feitosa Alves
  • Raimundo Fernandes de AraújoJr
Original Article

Abstract

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.

Keywords

Experimental periodontal disease Citocines Immunohistochemical Lipid peroxidant Olmesartan 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Aurigena Antunes Araújo
    • 1
  • Graziene Lopes de Souza
    • 2
  • Tatiana Oliveira Souza
    • 3
  • Gerly Anne de Castro Brito
    • 4
  • Karoline Sabóia Aragão
    • 5
  • Caroline Addison Xavier de Medeiros
    • 6
  • Yriu Lourenço
    • 7
  • Maria do Socorro Costa Feitosa Alves
    • 8
  • Raimundo Fernandes de AraújoJr
    • 9
  1. 1.Department of Biophysics and Pharmacology, UFRNPost graduation program Public Health / Post graduation program in Pharmaceutical ScienceNatalBrazil
  2. 2.Organization UFRN, Post graduation program in Pharmaceutical Science, UFRNNatalBrazil
  3. 3.Organization FACENE, Post graduation program Health Science, UFRNNatalBrazil
  4. 4.Organization UFC, Post graduation program in Pharmacology, UFCNatalBrazil
  5. 5.Organization UFC, Post-doc research position in Department of Pharmacology and Physiology, UFCNatalBrazil
  6. 6.Organization UERN, Post graduation program in Health and Society, UERNNatalBrazil
  7. 7.Organization UFRN, Department of Dentistry, UFRNNatalBrazil
  8. 8.Organization UFRN, Postgraduation program Health Science/Post graduation program Public Health,UFRNNatalBrazil
  9. 9.Organization UFRN, Post graduation program in Functional and Structural Biology/Post graduation program Health Science/Department of Morphology, UFRNNatalBrazil

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