Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos

Detalhes bibliográficos
Autor(a) principal: Dutra, Paula Góes Pinheiro
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/1993
Resumo: Periodontal disease is an infectious-inflammatory disease, and drugs have been studied as modulators of this inflammatory process. In this context, this thesis, constituted by 3 articles had by objective: (1) Perform a review about the effect of Bisphosphonates (BPs) on periodontal disease; (2) Investigate the effect of Alendronate (ALD) on Bone-specfic Alkaline Phosphatase (BALP) on alveolar bone loss (ABL) in rats; (3) Evaluate the effect of ALD and Atorvastatin (ATV) combination on ABL in rats. On study 1, we sought in data basis, using the keywords “Bisphosphonates” and “Periodontitis”, pre-clinical and clinical studies, published in English and Portuguese, in the last 10 years. On study 2, 36 Wistar male rats, submitted to ligature-induced periodontitis, received 0.9% Saline (SAL) or ALD on the doses of 0.01; 0.05; 0.25 mg/kg-s.c., 30 min before ligature placement and daily during 11 days. It was evaluated: ABL (morphometry and histology) serum levels of Bone-specific Alkaline Phosphatase (BALP), transaminases, and Total Alkaline Phosphatase (TAP); and leukogram and corporal mass. On study 3, 78 Wistar male rats, submitted to ligature-induced periodontitis, received prophylactically (P): SAL or ALD (0.01; 0.25 mg/kg-s.c) or ATV (0.3; 27 mg/kg-v.o.) or the combination ALD+ATV (0.25+27; 0.01+0.3; 0.25+0.3; 0.01+27 mg/kg), 30 min before ligature and daily for 11 days; or the combination ALD+ATV (0.01+0.3 mg/kg) administered therapeutically (T), from the 5th day after ligature until the sacrifice. It was evaluated: ABL [morphometry, histology, histometry; immunohistochemistry for tartrate resistant acid phosphatase (TRAP); myeloperoxidase (MPO); BALP, transaminases; Leukogram and corporal mass]. The study 1 showed that BPs presented anti-resorptive and anti-inflammatory effects, reduced FAO and Telopeptide N-terminal of type I collagen (NTx) and improved periodontal clinical parameters. On article 2, ALD (0.25 mg/kg) prevented BALP and ABL reduction, and did not alter transaminases serum levels, but reduced TAP serum levels (p<0.05), it reduced neutrophilia and lymphomonocytosis (p<0.05), without causing important loss of weight. On the 3rd study, the isolated treatments in high doses, and all combinations controlled ABL (p<0.05). Low doses combination of ALD+ATV controlled ABL (P [38.96%] or T [53.53%]). The histological, histometric (p<0.05) and immunohistochemical analysis corroborated macroscopical findings. The low dose combination of ALD+ATV reduced MPO activity, prevented BALP reduction, reduced neutrophilia and lymphomonocytosis (p<0.05), without altering transaminases serum levels and without causing loss of weight. In this way, we can conclude that BPs presented anti-resorptive and anti-inflammatory effects reduced levels of biochemical markers of bone metabolism and improved periodontal parameters. ALD, administered isolated prevented BALP and ABL reduction, without causing systemic problems, and the combination of ALD+ATV, in low doses, reduced ABL and periodontal inflammation, without causing important systemic alterations as well.
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spelling Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratosAnti-resorptive effect of Sodium Alendronate and the combination of Alendronate and atorvastatin in ligature-induced periodontitis in ratsAlendronatoPeriodontiteInflamaçãoPeriodontal disease is an infectious-inflammatory disease, and drugs have been studied as modulators of this inflammatory process. In this context, this thesis, constituted by 3 articles had by objective: (1) Perform a review about the effect of Bisphosphonates (BPs) on periodontal disease; (2) Investigate the effect of Alendronate (ALD) on Bone-specfic Alkaline Phosphatase (BALP) on alveolar bone loss (ABL) in rats; (3) Evaluate the effect of ALD and Atorvastatin (ATV) combination on ABL in rats. On study 1, we sought in data basis, using the keywords “Bisphosphonates” and “Periodontitis”, pre-clinical and clinical studies, published in English and Portuguese, in the last 10 years. On study 2, 36 Wistar male rats, submitted to ligature-induced periodontitis, received 0.9% Saline (SAL) or ALD on the doses of 0.01; 0.05; 0.25 mg/kg-s.c., 30 min before ligature placement and daily during 11 days. It was evaluated: ABL (morphometry and histology) serum levels of Bone-specific Alkaline Phosphatase (BALP), transaminases, and Total Alkaline Phosphatase (TAP); and leukogram and corporal mass. On study 3, 78 Wistar male rats, submitted to ligature-induced periodontitis, received prophylactically (P): SAL or ALD (0.01; 0.25 mg/kg-s.c) or ATV (0.3; 27 mg/kg-v.o.) or the combination ALD+ATV (0.25+27; 0.01+0.3; 0.25+0.3; 0.01+27 mg/kg), 30 min before ligature and daily for 11 days; or the combination ALD+ATV (0.01+0.3 mg/kg) administered therapeutically (T), from the 5th day after ligature until the sacrifice. It was evaluated: ABL [morphometry, histology, histometry; immunohistochemistry for tartrate resistant acid phosphatase (TRAP); myeloperoxidase (MPO); BALP, transaminases; Leukogram and corporal mass]. The study 1 showed that BPs presented anti-resorptive and anti-inflammatory effects, reduced FAO and Telopeptide N-terminal of type I collagen (NTx) and improved periodontal clinical parameters. On article 2, ALD (0.25 mg/kg) prevented BALP and ABL reduction, and did not alter transaminases serum levels, but reduced TAP serum levels (p<0.05), it reduced neutrophilia and lymphomonocytosis (p<0.05), without causing important loss of weight. On the 3rd study, the isolated treatments in high doses, and all combinations controlled ABL (p<0.05). Low doses combination of ALD+ATV controlled ABL (P [38.96%] or T [53.53%]). The histological, histometric (p<0.05) and immunohistochemical analysis corroborated macroscopical findings. The low dose combination of ALD+ATV reduced MPO activity, prevented BALP reduction, reduced neutrophilia and lymphomonocytosis (p<0.05), without altering transaminases serum levels and without causing loss of weight. In this way, we can conclude that BPs presented anti-resorptive and anti-inflammatory effects reduced levels of biochemical markers of bone metabolism and improved periodontal parameters. ALD, administered isolated prevented BALP and ABL reduction, without causing systemic problems, and the combination of ALD+ATV, in low doses, reduced ABL and periodontal inflammation, without causing important systemic alterations as well.A doença periodontal é uma desordem infecto-inflamatória, e fármacos têm sido estudados como moduladores deste processo inflamatório. Neste contexto, esta tese, constituída por 3 artigos, teve por objetivo: (1) Realizar uma revisão sobre o efeito de Bisfosfonatos (BFs) na doença periodontal; (2) Investigar o efeito do Alendronato (ALD) nos níveis de Fosfatase Alcalina Óssea (FAO) na perda óssea alveolar (POA) em ratos; (3) Avaliar o efeito da combinação entre ALD e Atorvastatina (ATV) na POA em ratos. No estudo 1 buscou-se, em bases de dados, utilizando as palavras chave: “Bisphosphonates” e “Periodontitis”, estudos pré-clínicos e clínicos, publicados em língua Inglesa ou Portuguesa, nos últimos 10 anos. No estudo 2, 36 ratos Wistar machos, submetidos à periodontite induzida por ligadura, receberam solução Salina (SAL) 0,9% ou ALD nas doses de 0,01; 0,05; 0,25 mg/kg-s.c, 30 min antes da colocação do fio e diariamente por 11 dias. Avaliou-se: POA (morfometria e histologia); níveis séricos de FAO, transaminases e Fosfatase Alcalina Total (FAT); Leucograma e Peso. No estudo 3, 78 ratos Wistar machos, submetidos à periodontite induzida por ligadura, receberam de forma profilática (P): SAL ou ALD (0,01; 0,25 mg/kg-s.c) ou ATV (0,3; 27 mg/kg-v.o.) ou a combinação ALD+ATV (0,25+27; 0,01+0,3; 0,25+0,3; 0,01+27 mg/kg), 30 min antes da ligadura e diariamente por 11 dias; ou ainda a combinação ALD+ATV (0,01+0,3 mg/kg) na forma terapêutica (T), ou seja administrada a partir do 5º dia após ligadura, até o sacrifício. Avaliou-se: POA [morfometria, histologia, histometria; imunohistoquímica para fosfatase ácido tártaro resistente (TRAP); mieloperoxidase (MPO); FAO, transaminases; Leucograma e Peso]. O artigo 1 mostrou que BFs apresentaram efeitos antirreabsortivo e anti-inflamatório, reduziram FAO e Telopeptídeo N-terminal de colágeno tipo I (NTx) e melhoraram os parâmetros clínicos periodontais. No artigo 2, o ALD (0,25 mg/kg) preveniu a redução de FAO e POA, não alterou níveis de transaminases, mas não preveniu redução dos níveis de FAT (p<0,05), preveniu neutrofilia e linfomonocitose (p<0,05), sem causar perda de peso importante. No 3º estudo, os tratamentos isolados, em altas doses, e todas as combinações avaliadas controlaram POA (p<0,05). A combinação de ALD+ATV em baixas doses controlou POA (P [38,96%] ou T [53,53%]). As análises histológicas, histométricas (p<0,05) e imunohistoquímicas corroboraram os achados macroscópicos. A combinação de ALD+ATV em baixas doses reduziu a atividade de MPO, preveniu redução de FAO, reduziu neutrofilia e linfomonocitose (p<0,05), sem alterar os níveis de transaminases e causar perda de peso. Desta forma conclui-se que os BFs apresentaram efeitos antirreabsortivo e anti-inflamatório, reduziram níveis de marcadores bioquímicos do metabolismo ósseo e melhoraram os parâmetros clínicos periodontais. O ALD, administrado isoladamente, preveniu redução de FAO, POA, sem repercussões sistêmicas e a combinação de ALD+ATV, em baixas doses, reduziu POA e inflamação periodontal, também sem causar alterações sistêmicas importantesLima, Vilma deDutra, Paula Góes Pinheiro2012-02-06T15:53:42Z2012-02-06T15:53:42Z2012info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfDUTRA, P. G. P. Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos. 101 f. 2012. Tese (Doutorado em Odontologia)- Universidade Federal do Ceará. Faculdade de Farmácia, Odontologia e Enfermagem, Fortaleza, 2012.http://www.repositorio.ufc.br/handle/riufc/1993porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-30T16:47:02Zoai:repositorio.ufc.br:riufc/1993Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:38:27.910999Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
Anti-resorptive effect of Sodium Alendronate and the combination of Alendronate and atorvastatin in ligature-induced periodontitis in rats
title Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
spellingShingle Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
Dutra, Paula Góes Pinheiro
Alendronato
Periodontite
Inflamação
title_short Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
title_full Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
title_fullStr Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
title_full_unstemmed Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
title_sort Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos
author Dutra, Paula Góes Pinheiro
author_facet Dutra, Paula Góes Pinheiro
author_role author
dc.contributor.none.fl_str_mv Lima, Vilma de
dc.contributor.author.fl_str_mv Dutra, Paula Góes Pinheiro
dc.subject.por.fl_str_mv Alendronato
Periodontite
Inflamação
topic Alendronato
Periodontite
Inflamação
description Periodontal disease is an infectious-inflammatory disease, and drugs have been studied as modulators of this inflammatory process. In this context, this thesis, constituted by 3 articles had by objective: (1) Perform a review about the effect of Bisphosphonates (BPs) on periodontal disease; (2) Investigate the effect of Alendronate (ALD) on Bone-specfic Alkaline Phosphatase (BALP) on alveolar bone loss (ABL) in rats; (3) Evaluate the effect of ALD and Atorvastatin (ATV) combination on ABL in rats. On study 1, we sought in data basis, using the keywords “Bisphosphonates” and “Periodontitis”, pre-clinical and clinical studies, published in English and Portuguese, in the last 10 years. On study 2, 36 Wistar male rats, submitted to ligature-induced periodontitis, received 0.9% Saline (SAL) or ALD on the doses of 0.01; 0.05; 0.25 mg/kg-s.c., 30 min before ligature placement and daily during 11 days. It was evaluated: ABL (morphometry and histology) serum levels of Bone-specific Alkaline Phosphatase (BALP), transaminases, and Total Alkaline Phosphatase (TAP); and leukogram and corporal mass. On study 3, 78 Wistar male rats, submitted to ligature-induced periodontitis, received prophylactically (P): SAL or ALD (0.01; 0.25 mg/kg-s.c) or ATV (0.3; 27 mg/kg-v.o.) or the combination ALD+ATV (0.25+27; 0.01+0.3; 0.25+0.3; 0.01+27 mg/kg), 30 min before ligature and daily for 11 days; or the combination ALD+ATV (0.01+0.3 mg/kg) administered therapeutically (T), from the 5th day after ligature until the sacrifice. It was evaluated: ABL [morphometry, histology, histometry; immunohistochemistry for tartrate resistant acid phosphatase (TRAP); myeloperoxidase (MPO); BALP, transaminases; Leukogram and corporal mass]. The study 1 showed that BPs presented anti-resorptive and anti-inflammatory effects, reduced FAO and Telopeptide N-terminal of type I collagen (NTx) and improved periodontal clinical parameters. On article 2, ALD (0.25 mg/kg) prevented BALP and ABL reduction, and did not alter transaminases serum levels, but reduced TAP serum levels (p<0.05), it reduced neutrophilia and lymphomonocytosis (p<0.05), without causing important loss of weight. On the 3rd study, the isolated treatments in high doses, and all combinations controlled ABL (p<0.05). Low doses combination of ALD+ATV controlled ABL (P [38.96%] or T [53.53%]). The histological, histometric (p<0.05) and immunohistochemical analysis corroborated macroscopical findings. The low dose combination of ALD+ATV reduced MPO activity, prevented BALP reduction, reduced neutrophilia and lymphomonocytosis (p<0.05), without altering transaminases serum levels and without causing loss of weight. In this way, we can conclude that BPs presented anti-resorptive and anti-inflammatory effects reduced levels of biochemical markers of bone metabolism and improved periodontal parameters. ALD, administered isolated prevented BALP and ABL reduction, without causing systemic problems, and the combination of ALD+ATV, in low doses, reduced ABL and periodontal inflammation, without causing important systemic alterations as well.
publishDate 2012
dc.date.none.fl_str_mv 2012-02-06T15:53:42Z
2012-02-06T15:53:42Z
2012
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dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.uri.fl_str_mv DUTRA, P. G. P. Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos. 101 f. 2012. Tese (Doutorado em Odontologia)- Universidade Federal do Ceará. Faculdade de Farmácia, Odontologia e Enfermagem, Fortaleza, 2012.
http://www.repositorio.ufc.br/handle/riufc/1993
identifier_str_mv DUTRA, P. G. P. Efeito antirreabsortivo do alendronato e da combinação entre alendronato e atorvastatina na periodontite induzida por ligadura em ratos. 101 f. 2012. Tese (Doutorado em Odontologia)- Universidade Federal do Ceará. Faculdade de Farmácia, Odontologia e Enfermagem, Fortaleza, 2012.
url http://www.repositorio.ufc.br/handle/riufc/1993
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