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.

Aurigena Antunes De Araújo,Raimundo Fernandes De Araújo Júnior,Caroline Addison Carvalho Xavier De Medeiros,José Heriberto Oliveira Do Nascimento,Gerly Anne De Castro Brito,Lorena De Souza Araújo,Hugo Varela

doi:10.1371/journal.pone.0096750

Aurigena Antunes De Araújo, Raimundo Fernandes De Araújo Júnior + Show 5 more

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https://doi.org/10.1371/journal.pone.0096750

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Journal: PloS one	Publication Date: May 12, 2014
Citations: 29	License type: CC BY 4.0

Affiliation: Universidade Federal do Rio Grande do Norte

Abstract

AimsThe 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 MethodsMale 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.ResultsTreatment 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.ConclusionsThese findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

Highlights

Periodontal disease is a chronic infectious, inflammatory disease of the gums and supporting tissues
Treatment with 5 mg/kg AZT resulted in reduced MPO (p,0.05) and IL-1b (p,0.05), increased levels of IL-10 (p, 0.05), and reduced expression of matrix metallo proteinases (MMPs)-2, MMP-9, COX-2, receptor activator of nuclear factor kB (RANK), receptor activator of nuclear factor kB ligand (RANKL), cathepsin K, and increased expression of OPG
These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats

Summary

Introduction

Periodontal disease is a chronic infectious, inflammatory disease of the gums and supporting tissues. Several modulating agents have been investigated as potential therapies for periodontal disease, including antiproteinases, anti-inflammatory drugs, and bone-sparing drugs [1]. Improved knowledge of the mechanisms involved in the pathogenesis of periodontal disease have led to the use of novel agents to modulate the host response by inhibiting inflammatory mediators. Studies with antihypertensive drugs have shown that they have an anti-inflammatory activity in periodontal disease with reduced bone loss [2,3,4,5]. Our group have study the angiotensin II receptor blocker (ARB). The angiotensin II receptor blocker (ARB) has been implicated as an anti-inflammatory agent that suppresses tumor necrosis factor (TNF)-a-induced activation of nuclear factor (NF)-kB in vascular endothelial cells [6]

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