Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos

Detalhes bibliográficos
Autor(a) principal: Kurita, Bianca Moreira
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/21898
Resumo: The induced tooth movement (ITM) combines bone resorption and neoformation that depends on chemical mediators of inflammation, thus culminating in bone remodeling. This observation has encouraged the evaluation of the effect of zoledronic acid (ZOL), a bisphosphonate that inhibits osteoclastic activity, being widely used for treating bone metabolic disorders, such as osteoporosis and bone metastasis. However, literature has not addresses the participations of proinflammatory cytokines on RANKL-OPG axis modulation during MDI and ZOL treatment. On this, we evaluated the effect of ZOL on bone remodeling of ITM. ITM was performed in 72 anesthetized Wistar rats by the installation and activation of a nickel-titanium coil-spring, with 50 gf, fixed on upper left 1st molar and upper incisors. The same received distilled water, being considered as non-treated group (NT - 1 ml/kg-i.v.) or ZOL (50, 100 e 200 g/kg-iv), 5 minutes before the dispositive insertion, and on 7th day. On day zero, blood samples were collected for leukogram assay (mm3) and bone alkaline phosphatase dosage (BALP: U/I), and the space between the teeth were measured. On the 11th day, the collects and measures were repeated and the gingivas and hemimaxillas were removed for myeloperoxidase activity dosage (MPO: 103 mg of tissue) and TNF- e IL-1 gingival levels analysis (pg/mg of tissue), histomorphometric analysis of periodontal ligament areas of compression, traction and hyalines, histological evaluation by scores (0 to 3) of root and bone resorptions and immunohistochemical staining for RANKL, OPG, TRAP, TNF- e IL-1. The animals were weighted daily during the all-experimental period, and then, were related to basal values; Ethics Committee on the Use of Animals-UFC nº 28/15. The NT group, had an increase of tooth movement, high scores of root and bone resorption, increased activity of MPO and high gingival levels of TNF- e IL-1, intense immunostaining for RANKL, TRAP e TNF- on the compression side and for RANKL and OPG on the traction side of periodontal ligament, resulting on increased RANKL/OPG ratio on compression side (p<0.05). Still, they do not presented changes in serum levels of BALP, in total and differential leukogram assay and histomorphometric analysis (p>0.05), but they lost weight initially, being the initial weight, recovered from the 7th day. ZOL treatment in three doses used reduced tooth movement in a dose-dependent manner, as well as resulted in low scores of root and bone resorption and reduction of MPO activity. However, ZOL in the high dose (200 g/kg) did not change TNF- e IL-1 gingival levels (p>0.05). Still, this dose reduced the immunostaining of TRAP on compression side, OPG on traction side and RANKL and TNF- on both sides, resulting on a decrease of RANKL/OPG ratio on both regions analyzed (p<0.05). In addition, ZOL treatment did not induce changes on leukogram values and body mass variation in comparison to the animals that received dH2O (p>0.05). In short, ZOL reduced the ITM by decreasing bone biomarkers essential for osteoclastic differentiation and activity and reducing bone anabolism.
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spelling Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratosBone anti-inflammatory and antirreabsortive activities of zoledronic acid during induced tooth moovement in ratsMovimentação DentáriaRemodelação ÓsseaOsteoclastosThe induced tooth movement (ITM) combines bone resorption and neoformation that depends on chemical mediators of inflammation, thus culminating in bone remodeling. This observation has encouraged the evaluation of the effect of zoledronic acid (ZOL), a bisphosphonate that inhibits osteoclastic activity, being widely used for treating bone metabolic disorders, such as osteoporosis and bone metastasis. However, literature has not addresses the participations of proinflammatory cytokines on RANKL-OPG axis modulation during MDI and ZOL treatment. On this, we evaluated the effect of ZOL on bone remodeling of ITM. ITM was performed in 72 anesthetized Wistar rats by the installation and activation of a nickel-titanium coil-spring, with 50 gf, fixed on upper left 1st molar and upper incisors. The same received distilled water, being considered as non-treated group (NT - 1 ml/kg-i.v.) or ZOL (50, 100 e 200 g/kg-iv), 5 minutes before the dispositive insertion, and on 7th day. On day zero, blood samples were collected for leukogram assay (mm3) and bone alkaline phosphatase dosage (BALP: U/I), and the space between the teeth were measured. On the 11th day, the collects and measures were repeated and the gingivas and hemimaxillas were removed for myeloperoxidase activity dosage (MPO: 103 mg of tissue) and TNF- e IL-1 gingival levels analysis (pg/mg of tissue), histomorphometric analysis of periodontal ligament areas of compression, traction and hyalines, histological evaluation by scores (0 to 3) of root and bone resorptions and immunohistochemical staining for RANKL, OPG, TRAP, TNF- e IL-1. The animals were weighted daily during the all-experimental period, and then, were related to basal values; Ethics Committee on the Use of Animals-UFC nº 28/15. The NT group, had an increase of tooth movement, high scores of root and bone resorption, increased activity of MPO and high gingival levels of TNF- e IL-1, intense immunostaining for RANKL, TRAP e TNF- on the compression side and for RANKL and OPG on the traction side of periodontal ligament, resulting on increased RANKL/OPG ratio on compression side (p<0.05). Still, they do not presented changes in serum levels of BALP, in total and differential leukogram assay and histomorphometric analysis (p>0.05), but they lost weight initially, being the initial weight, recovered from the 7th day. ZOL treatment in three doses used reduced tooth movement in a dose-dependent manner, as well as resulted in low scores of root and bone resorption and reduction of MPO activity. However, ZOL in the high dose (200 g/kg) did not change TNF- e IL-1 gingival levels (p>0.05). Still, this dose reduced the immunostaining of TRAP on compression side, OPG on traction side and RANKL and TNF- on both sides, resulting on a decrease of RANKL/OPG ratio on both regions analyzed (p<0.05). In addition, ZOL treatment did not induce changes on leukogram values and body mass variation in comparison to the animals that received dH2O (p>0.05). In short, ZOL reduced the ITM by decreasing bone biomarkers essential for osteoclastic differentiation and activity and reducing bone anabolism.A movimentação dentária induzida (MDI) combina respostas de reabsorção e neoformação ósseas, que dependem da atividade de mediadores químicos da inflamação, culminando em remodelação óssea. Tal observação tem incentivado a avaliação do efeito do ácido zoledrônico (ZOL), um bisfosfonato que inibe a atividade osteoclástica, sendo amplamente utilizado para tratamento de desordens metabólicas ósseas, como a osteoporose e metástases ósseas. Contudo a literatura não tem abordado a participação de citocinas pró-inflamatórias e a modulação do eixo RANKL-OPG durante a MDI e tratamento com ZOL. Diante, disso, avaliou-se o efeito do ZOL na remodelação óssea da MDI. A MDI foi realizada em 72 ratos Wistar anestesiados pela instalação e ativação de uma mola fechada de níquel-titânio com 50 gf, fixada ao 1° molar superior esquerdo e aos incisivos superiores. Os mesmos receberam H2O destilada, sendo considerados animais não tratados (NT - 1 ml/kg-i.v.) ou ZOL (50, 100 e 200 g/kg-i.v.), 5 min antes da inserção do dispositivo, e no 7º dia. No dia zero, foram coletadas amostras sanguíneas para avaliação do leucograma (mm3 de sangue) e dosagem de fosfatase alcalina óssea (FAO: U/I) e mensurados os espaços entre os dentes. No 11º dia, as coletas e as mensurações foram repetidas e as gengivas e hemiarcadas removidas para as avaliações da atividade da mieloperoxidase (MPO: x 103 mg de gengiva) e dos níveis de TNF- e IL-1 (pg/mg de gengiva), análise histomorfométrica das áreas de compressão, tração e hialinas do ligamento periodontal (LP), análise histológica por escores (0 a 3) das reabsorções radicular (RR) e óssea (RO) e análise imunohistoquímica para RANKL, OPG, TRAP e TNF-. Os animais foram pesados diariamente durante todo o período experimental, sendo os valores encontrados, relacionados à massa do dia zero; Comissão de Ética no Uso de Animais-UFC nº 28/15. O grupo NT apresentou aumento do deslocamento dentário, escores altos para as RR e RO, aumento da atividade de MPO e dos níveis gengivais de TNF- e IL-1, maior imunomarcação para RANKL, TRAP e TNF- no lado de compressão do LP e para RANKL e OPG no lado de tração, resultando em aumento da razão RANKL/OPG no lado de compressão (p<0,05). Não apresentaram alterações nos níveis séricos de FAO, leucograma e na análise histomorfométrica (p>0,05), mas perderam peso inicialmente, alcançado os valores basais ao 7º dia. O tratamento com ZOL nas três doses reduziu o movimento dentário de forma dose-dependente, bem como reduziuos escores de RR e RO e a atividade de MPO (p<0,05). No entanto, a maior dose de ZOL (200 g/kg) não alterou os níveis gengivais de TNF- e IL-1 (p>0,05). Nessa mesma dose, o ZOL reduziu a imunomarcação para TRAP no lado de compressão, OPG no lado de tração e RANKL e TNF- em ambos os lados, resultando em decréscimo na razão RANKL/OPG nas duas regiões avaliadas (p<0,05). Ademais, o tratamento com o ZOL não induziu alterações do leucograma e não promoveu perda de peso significante em relação aos animais não tratados (p>0,05). Em suma, o ZOL reduziu a MDI por meio da inibição de biomarcadores ósseos essenciais à diferenciação e atividade osteoclástica e redução do anabolismo ósseo.Lima , Vilma deKurita, Bianca Moreira2017-02-06T13:27:15Z2017-02-06T13:27:15Z2017-01-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfKURITA, B. M. Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos. 2017. 109 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2017.http://www.repositorio.ufc.br/handle/riufc/21898porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-10-18T12:08:16Zoai:repositorio.ufc.br:riufc/21898Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:25:56.457875Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
Bone anti-inflammatory and antirreabsortive activities of zoledronic acid during induced tooth moovement in rats
title Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
spellingShingle Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
Kurita, Bianca Moreira
Movimentação Dentária
Remodelação Óssea
Osteoclastos
title_short Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
title_full Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
title_fullStr Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
title_full_unstemmed Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
title_sort Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos
author Kurita, Bianca Moreira
author_facet Kurita, Bianca Moreira
author_role author
dc.contributor.none.fl_str_mv Lima , Vilma de
dc.contributor.author.fl_str_mv Kurita, Bianca Moreira
dc.subject.por.fl_str_mv Movimentação Dentária
Remodelação Óssea
Osteoclastos
topic Movimentação Dentária
Remodelação Óssea
Osteoclastos
description The induced tooth movement (ITM) combines bone resorption and neoformation that depends on chemical mediators of inflammation, thus culminating in bone remodeling. This observation has encouraged the evaluation of the effect of zoledronic acid (ZOL), a bisphosphonate that inhibits osteoclastic activity, being widely used for treating bone metabolic disorders, such as osteoporosis and bone metastasis. However, literature has not addresses the participations of proinflammatory cytokines on RANKL-OPG axis modulation during MDI and ZOL treatment. On this, we evaluated the effect of ZOL on bone remodeling of ITM. ITM was performed in 72 anesthetized Wistar rats by the installation and activation of a nickel-titanium coil-spring, with 50 gf, fixed on upper left 1st molar and upper incisors. The same received distilled water, being considered as non-treated group (NT - 1 ml/kg-i.v.) or ZOL (50, 100 e 200 g/kg-iv), 5 minutes before the dispositive insertion, and on 7th day. On day zero, blood samples were collected for leukogram assay (mm3) and bone alkaline phosphatase dosage (BALP: U/I), and the space between the teeth were measured. On the 11th day, the collects and measures were repeated and the gingivas and hemimaxillas were removed for myeloperoxidase activity dosage (MPO: 103 mg of tissue) and TNF- e IL-1 gingival levels analysis (pg/mg of tissue), histomorphometric analysis of periodontal ligament areas of compression, traction and hyalines, histological evaluation by scores (0 to 3) of root and bone resorptions and immunohistochemical staining for RANKL, OPG, TRAP, TNF- e IL-1. The animals were weighted daily during the all-experimental period, and then, were related to basal values; Ethics Committee on the Use of Animals-UFC nº 28/15. The NT group, had an increase of tooth movement, high scores of root and bone resorption, increased activity of MPO and high gingival levels of TNF- e IL-1, intense immunostaining for RANKL, TRAP e TNF- on the compression side and for RANKL and OPG on the traction side of periodontal ligament, resulting on increased RANKL/OPG ratio on compression side (p<0.05). Still, they do not presented changes in serum levels of BALP, in total and differential leukogram assay and histomorphometric analysis (p>0.05), but they lost weight initially, being the initial weight, recovered from the 7th day. ZOL treatment in three doses used reduced tooth movement in a dose-dependent manner, as well as resulted in low scores of root and bone resorption and reduction of MPO activity. However, ZOL in the high dose (200 g/kg) did not change TNF- e IL-1 gingival levels (p>0.05). Still, this dose reduced the immunostaining of TRAP on compression side, OPG on traction side and RANKL and TNF- on both sides, resulting on a decrease of RANKL/OPG ratio on both regions analyzed (p<0.05). In addition, ZOL treatment did not induce changes on leukogram values and body mass variation in comparison to the animals that received dH2O (p>0.05). In short, ZOL reduced the ITM by decreasing bone biomarkers essential for osteoclastic differentiation and activity and reducing bone anabolism.
publishDate 2017
dc.date.none.fl_str_mv 2017-02-06T13:27:15Z
2017-02-06T13:27:15Z
2017-01-16
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv KURITA, B. M. Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos. 2017. 109 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2017.
http://www.repositorio.ufc.br/handle/riufc/21898
identifier_str_mv KURITA, B. M. Atividades anti-inflamatória e antirreabsortiva ósseas do ácido zoledrônico durante a movimentação dentária induzida em ratos. 2017. 109 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2017.
url http://www.repositorio.ufc.br/handle/riufc/21898
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