Efeitos da azilsartana sobre a doença periodontal em um modelo experimental com ratos wistar / Effects of azilsartan on periodontal disease in an experimental model in Wistar rats

RESUMO

As doenças periodontais possuem alta prevalência na população mundial e manifestam-se, principalmente, em duas entidades distintas, a saber a gengivite induzida pela placa bacteriana e a periodontite. A periodontite é uma doença inflamatória crônica caracterizada pela destruição em vários níveis do osso alveolar, fibras colágenas e do cemento, é considerada importante causa de perda dentária em adultos. Estudos experimentais recentes demonstram o efeito anti-inflamatório e antirreabsortivo dos fármacos anti-hipertensivos da classe dos bloqueadores dos receptores de angiotensina II sobre a doença periodontal. O objetivo desse estudo foi avaliar os efeitos da azilsartana (AZT) um potente inibidor dos receptores de angiotensina II que apresenta efeitos adversos mínimos, sobre a perda óssea alveolar, inflamação, expressão das metaloproteinases da matriz (MMP), ligante do receptor do fator nuclear kapa B (RANKL), receptor ativador do fator nuclear kapa B (RANK), osteoprotegerina (OPG), ciclooxigenase-2 (COX-2), Interleucina 10, Interleucina 1β, TNF-α, glutationa (GSH) e catepsina K no modelo de doença periodontal induzida por ligadura em ratos.

ABSTRACT

Periodontal diseases, highly prevalent disease in worldwide population, manifest primarily in two distinct entities plaque-induced gingivitis and periodontitis. Periodontitis is a chronic inflammatory disease characterized of different levels of collagen, cementum, and alveolar bone destruction. Recent experimental studies demonstrated anti-inflammatory and antirreabsortive effect of antihypertensive agents of the angiotensin II receptor blockers class on periodontal disease. The aim of this study was to evaluate the effects of azilsartan (AZT), a potent inhibitor of the angiotensin II receptor which has minimal adverse effects on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor kB ligand (RANKL), receptor activator of nuclear factor kB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. Male Wistar albino rats were randomly divided into 5 groups of 20 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 water or AZT for 10 days. Periodontal tissues were analyzed by morphometric exam, histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1b, IL-10, TNF-a, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA. Treatment with 5 mg/kg AZT resulted in reduced MPO (p˂0.05) and IL-1b (p˂0.05) levels and increased in Il-10 levels (p˂0.05). It was observed a reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and a increased expression of OPG in the animals subjected to experimental periodontitis and threated with AZT (5 mg/kg). Conclusions: These findings suggest an anti-inflammatory and anti-reabsortive effects of AZT on ligature-induced periodontitis in rats. (AU)