Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-23T00:15:56Z No. of bitstreams: 1 HugoDeAlmeidaVarela_DISSERT.pdf: 3160219 bytes, checksum: 5e75a6e4f85482a68335030d7da0f1e7 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-26T23:37:36Z (GMT) No. of bitstreams: 1 HugoDeAlmeidaVarela_DISSERT.pdf: 3160219 bytes, checksum: 5e75a6e4f85482a68335030d7da0f1e7 (MD5) / Made available in DSpace on 2016-02-26T23:37:36Z (GMT). No. of bitstreams: 1 HugoDeAlmeidaVarela_DISSERT.pdf: 3160219 bytes, checksum: 5e75a6e4f85482a68335030d7da0f1e7 (MD5) Previous issue date: 2015-03-19 / As doen?as periodontais possuem alta preval?ncia na popula??o mundial e manifestam-se, principalmente, em duas entidades distintas, a saber: a gengivite induzida pela placa bacteriana e a periodontite. A periodontite ? uma doen?a inflamat?ria cr?nica caracterizada pela destrui??o em v?rios n?veis do osso alveolar, fibras col?genas e do cemento, ? considerada importante causa de perda dent?ria em adultos. Estudos experimentais recentes demonstram o efeito anti-inflamat?rio e antirreabsortivo dos f?rmacos anti-hipertensivos da classe dos bloqueadores dos receptores de angiotensina II sobre a doen?a periodontal. O objetivo desse estudo foi avaliar os efeitos da azilsartana (AZT) um potente inibidor dos receptores de angiotensina II que apresenta efeitos adversos m?nimos, sobre a perda ?ssea alveolar, inflama??o, express?o 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 1?, TNF-?, glutationa (GSH) e catepsina K no modelo de doen?a periodontal induzida por ligadura em ratos. Foram utilizados 100 ratos wistar sendo divididos randomicamente em 5 grupos com 20 ratos cada: (1) n?o foi induzida a doen?a periodontal, ?gua destilada, (2) indu??o da doen?a periodontal, ?gua destilada; (3) indu??o da doen?a periodontal, AZT 1 mg/kg; (4) indu??o da doen?a periodontal, AZT 5 mg/kg; e (5) indu??o da doen?a periodontal, AZT 10 mg/kg. Todos os grupos foram tratados com ?gua destilada ou AZT por 10 dias. Os tecidos periodontais foram submetidos ?s an?lises morfom?trica, histopatol?gica e imunohistoqu?mica para detec??o de MMP-2, MMP-9, RANKL, RANK, OPG e catepsina K. N?veis de IL-1?, IL-10, TNF-? foram determinados por ELISA e n?veis de mieloperoxidase(MPO) e glutationa(GSH) por espectrofotoscopia de UV vis?vel. O tratamento com AZT 5 mg/kg reduziu o MPO (p <0.05) e IL-1? (p <0.05), elevou os n?veis de IL-10 (p <0.05), reduziu a express?o de MMP-2, MMP-9, RANK, RANKL, catepsina K, e elevou a express?o de OPG. Os achados revelam que a AZT na dosagem 5mg/kg apresenta a??o anti-inflamat?ria na doen?a periodontal induzida por ligadura reduzindo a perda ?ssea alveolar, diminuindo os n?veis de citocinas pr?-inflamat?rias e elevando a express?o de agentes anti-inflamat?rios. / 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.