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

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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.

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Authors and Affiliations

  1. Department of Biophysics and Pharmacology, UFRN, Post graduation program Public Health / Post graduation program in Pharmaceutical Science, Natal, RN, Brazil

    Aurigena Antunes Araújo

  2. Organization UFRN, Post graduation program in Pharmaceutical Science, UFRN, Natal, RN, Brazil

    Graziene Lopes de Souza

  3. Organization FACENE, Post graduation program Health Science, UFRN, Natal, RN, Brazil

    Tatiana Oliveira Souza

  4. Organization UFC, Post graduation program in Pharmacology, UFC, Natal, RN, Brazil

    Gerly Anne de Castro Brito

  5. Organization UFC, Post-doc research position in Department of Pharmacology and Physiology, UFC, Natal, RN, Brazil

    Karoline Sabóia Aragão

  6. Organization UERN, Post graduation program in Health and Society, UERN, Natal, RN, Brazil

    Caroline Addison Xavier de Medeiros

  7. Organization UFRN, Department of Dentistry, UFRN, Natal, RN, Brazil

    Yriu Lourenço

  8. Organization UFRN, Postgraduation program Health Science/Post graduation program Public Health,UFRN, Natal, RN, Brazil

    Maria do Socorro Costa Feitosa Alves

  9. Organization UFRN, Post graduation program in Functional and Structural Biology/Post graduation program Health Science/Department of Morphology, UFRN, Natal, RN, Brazil

    Raimundo Fernandes de Araújo Jr

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  1. Aurigena Antunes Araújo
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  2. Graziene Lopes de Souza
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  3. Tatiana Oliveira Souza
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  4. Gerly Anne de Castro Brito
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  5. Karoline Sabóia Aragão
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  6. Caroline Addison Xavier de Medeiros
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  8. Maria do Socorro Costa Feitosa Alves
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  9. Raimundo Fernandes de Araújo Jr
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Correspondence to Aurigena Antunes Araújo.

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Araújo, A.A., Lopes de Souza, G., Souza, T.O. et al. Olmesartan decreases IL-1β and TNF-α levels; downregulates MMP-2, MMP-9, COX-2, and RANKL; and upregulates OPG in experimental periodontitis. Naunyn-Schmiedeberg's Arch Pharmacol 386, 875–884 (2013). https://doi.org/10.1007/s00210-013-0886-8

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  • DOI: https://doi.org/10.1007/s00210-013-0886-8

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