Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.

Detalhes bibliográficos
Autor(a) principal: Silvana MagalhÃes Siqueira Menezes
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8728
Resumo: The immune/inflammatory response has a key role in the periodontal disease (DP) whose progression results from an imbalance between periodontopathogenic microorganisms and the host response. This leads to the production and release of inflammatory mediators and tissue damage. DP is considered the sixth complication in diabetes. Furthermore, diabetes mellitus and periodontitis present common links related to inflammation processes and immunologic system stimuli and, in the presence of diabetes with uncontrolled insulin levels, the aggravation of preexistant periodontitis may occur. Also, DP may reciprocally aggravate the diabetic state. Minocycline (M) is a second generation tetracycline showing anti-inflammatory effects independent of its antimicrobial action. The objectives of the present work were to investigate the effects of M (25 and 50 mg/kg, p.o.) in an experimental model of periodontal disease (DPE), in the presence and absence of alloxan-induced diabetes (DIA) in rats. DPE was induced through a nylon thread insertion and ligation in the second superior molar of male Wistar rats (200 g).For histological analyses and measurements of biochemical parameters, as glycemia, cholesterol, triglycerides and liver transaminases (ALT and AST) the groups (n=6) were divided : DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 and DPE+DIA+M50. After 11 or 30 days the animals were sacrificed. . Immunohitochemistry for TNF-α, iNOS and MMP-9 was performed in groups (n=4): DPE; DPE+DIA; DPE+M50; and DPE+DIA+M50. After 11 days the animals were sacrificed. The results showed that M50 presents a potent anti-inflammatory activity, preserving the alveolar and cement bones in the DPE and DPE+DIA models, after both periods of time. Under these experimental conditions, M50 also significantly reduced blood glucose levels. Furthermore, M50 reduced imunnostainings for TNF-α, iNOS and MMP-9. M25 did not significantly reduce the inflammatory process in DPE animals sacrificed at the 11th day after DPE induction.In addition, levels of triglycerides and total cholesterol were reduced in the DPE model, in the presence and absence of diabetes, after M25 and M50 treatments. Our data demonstrated that minocycline at both doses was well tolerated, and no significant alterations in ALT levels were observed in the DPE and DPE+DIA groups, at the 11th and 30th day, as well as on the levels of AST in groups DPE (11th day). However, the DPE + DIA group treated with M50 for 30 days presented a significant increase in AST levels. Our results strongly suggest that minocycline could be used for the periodontal disease treatment, since it protects the periodontium and reduces glycemia levels in the presence of the diabetic state. These beneficial effects are probably related to the potent anti-inflammatory properties of this drug, point out to its potential as an alternative for the treatment of diseases where the inflammatory process play a key role.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisEfeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.Anti-inflammatory and anti resorptive bone effects of minocycline in periodontal disease induced in normal and diabetic rats.2012-06-22Glauce Socorro de Barros Viana00101761368http://lattes.cnpq.br/5043495454602083Renata Ferreira de Carvalho LeitÃo43088139304http://lattes.cnpq.br/5213035069793195Ana Paula Negreiros Nunes Alves19242662372http://lattes.cnpq.br/5522921433940881 AntÃnio Josà Lapa04650816815http://lattes.cnpq.br/8371393564245194 MÃrcia Maria de Negreiros Pinto Rocha46546529300http://lattes.cnpq.br/2888374721836380 47992506391http://lattes.cnpq.br/9239964700549050Silvana MagalhÃes Siqueira MenezesUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBRFARMACOLOGIAThe immune/inflammatory response has a key role in the periodontal disease (DP) whose progression results from an imbalance between periodontopathogenic microorganisms and the host response. This leads to the production and release of inflammatory mediators and tissue damage. DP is considered the sixth complication in diabetes. Furthermore, diabetes mellitus and periodontitis present common links related to inflammation processes and immunologic system stimuli and, in the presence of diabetes with uncontrolled insulin levels, the aggravation of preexistant periodontitis may occur. Also, DP may reciprocally aggravate the diabetic state. Minocycline (M) is a second generation tetracycline showing anti-inflammatory effects independent of its antimicrobial action. The objectives of the present work were to investigate the effects of M (25 and 50 mg/kg, p.o.) in an experimental model of periodontal disease (DPE), in the presence and absence of alloxan-induced diabetes (DIA) in rats. DPE was induced through a nylon thread insertion and ligation in the second superior molar of male Wistar rats (200 g).For histological analyses and measurements of biochemical parameters, as glycemia, cholesterol, triglycerides and liver transaminases (ALT and AST) the groups (n=6) were divided : DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 and DPE+DIA+M50. After 11 or 30 days the animals were sacrificed. . Immunohitochemistry for TNF-α, iNOS and MMP-9 was performed in groups (n=4): DPE; DPE+DIA; DPE+M50; and DPE+DIA+M50. After 11 days the animals were sacrificed. The results showed that M50 presents a potent anti-inflammatory activity, preserving the alveolar and cement bones in the DPE and DPE+DIA models, after both periods of time. Under these experimental conditions, M50 also significantly reduced blood glucose levels. Furthermore, M50 reduced imunnostainings for TNF-α, iNOS and MMP-9. M25 did not significantly reduce the inflammatory process in DPE animals sacrificed at the 11th day after DPE induction.In addition, levels of triglycerides and total cholesterol were reduced in the DPE model, in the presence and absence of diabetes, after M25 and M50 treatments. Our data demonstrated that minocycline at both doses was well tolerated, and no significant alterations in ALT levels were observed in the DPE and DPE+DIA groups, at the 11th and 30th day, as well as on the levels of AST in groups DPE (11th day). However, the DPE + DIA group treated with M50 for 30 days presented a significant increase in AST levels. Our results strongly suggest that minocycline could be used for the periodontal disease treatment, since it protects the periodontium and reduces glycemia levels in the presence of the diabetic state. These beneficial effects are probably related to the potent anti-inflammatory properties of this drug, point out to its potential as an alternative for the treatment of diseases where the inflammatory process play a key role. A resposta imune/inflamatÃria tem um papel fundamental na doenÃa periodontal (DP), onde a progressÃo à decorrente de um desequilÃbrio entre as bactÃrias periodontopatogÃnicas e a resposta do hospedeiro frente à agressÃo, com produÃÃo e liberaÃÃo de mediadores e subseqÃente dano tecidual. A DP à considerada a sexta complicaÃÃo clÃssica do diabetes. O diabetes mellitus e a periodontite possuem aspectos comuns no Ãmbito do estÃmulo inflamatÃrio e imunolÃgico, constituindo uma via de mÃo dupla, onde a primeira nÃo estando com sua taxa insulÃnica compensada poderà agravar uma periodontite preexistente e vice-versa. A minociclina(M) à uma tetraciclina de segunda geraÃÃo que apresenta efeitos anti-inflamatÃrios independentes de sua aÃÃo antimicrobiana. Os objetivos do presente estudo foram investigar os efeitos da M (25 e 50 mg/kg, via oral) em um modelo experimental de doenÃa periodontal (DPE), na presenÃa e ausÃncia de diabetes (DIA) induzida por aloxano em ratos. A DPE foi induzida passando-se um fio de nÃilon em torno do segundo molar superior esquerdo de ratos machos Wistar (200 g). Para as anÃlises histolÃgicas e determinaÃÃo dos parÃmetros bioquÃmicos, como glicemia, colesterol, triglicerÃdeos e enzimas hepÃticas (ALT e AST), os grupos (n=6) foram divididos em: DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 e DPE+DIA+M50. ApÃs 11 e 30 dias os animais foram sacrificados. A imunohistoquÃmica para TNF-α, iNOS e MMP-9 foi realizada nos grupos(n=4): DPE; DPE+DIA; DPE+M50 e DPE+DIA+M50. Os animais foram sacrificados apÃs 11 dias. Os resultados mostraram que a M50 apresenta potente atividade anti-inflamatÃria, preservando o osso alveolar e cemento, nos modelos experimentais de DPE e DPE + DIA, em ambos os perÃodos de estudo. Nestas mesmas condiÃÃes experimentais, a M50 tambÃm reduziu significantemente os nÃveis sanguÃneos de glicose. A M50 tambÃm reduziu a imunomarcaÃÃo para TNF-α, iNOS e MMP-9. A M25 nÃo reduziu o processo inflamatÃrio nos animais com DPE, sacrificados no 11 dia. Os nÃveis de triglicerÃdeos e colesterol total foram reduzidos nos modelos experimentais de DPE e de DPE + DIA, tratados com M25 e M50. Nossos resultados demonstraram que a minociclina em ambas as doses foi bem tolerada, sem alteraÃÃes significativas sobre os nÃveis de ALT, assim como sobre os nÃveis de AST nos grupos DPE (11 dia). Entretanto, o grupo DPE + DIA tratado com M50 por 30 dias, apresentou um aumento significativo na atividade da AST. Nossos resultados sugerem fortemente que a minociclina pode ser usada para o tratamento da doenÃa periodontal, tendo em vista que protege o periodonto e reduz nÃveis de glicemia na presenÃa do estado diabÃtico. Estes efeitos benÃficos sÃo provavelmente decorrentes das propriedades anti-inflamatÃrias desta droga, que surge como um potente tratamento alternativo para doenÃas onde o processo inflamatÃrio tem um papel fundamental.CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superiorhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8728application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:21:35Zmail@mail.com -
dc.title.pt.fl_str_mv Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
dc.title.alternative.en.fl_str_mv Anti-inflammatory and anti resorptive bone effects of minocycline in periodontal disease induced in normal and diabetic rats.
title Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
spellingShingle Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
Silvana MagalhÃes Siqueira Menezes
FARMACOLOGIA
title_short Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
title_full Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
title_fullStr Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
title_full_unstemmed Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
title_sort Efeitos anti-inflamatÃrios e antirreabsortivo Ãsseo da minociclina na doenÃa periodontal induzida em ratos diabÃticos e normais.
author Silvana MagalhÃes Siqueira Menezes
author_facet Silvana MagalhÃes Siqueira Menezes
author_role author
dc.contributor.advisor1.fl_str_mv Glauce Socorro de Barros Viana
dc.contributor.advisor1ID.fl_str_mv 00101761368
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5043495454602083
dc.contributor.referee1.fl_str_mv Renata Ferreira de Carvalho LeitÃo
dc.contributor.referee1ID.fl_str_mv 43088139304
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/5213035069793195
dc.contributor.referee2.fl_str_mv Ana Paula Negreiros Nunes Alves
dc.contributor.referee2ID.fl_str_mv 19242662372
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/5522921433940881
dc.contributor.referee3.fl_str_mv AntÃnio Josà Lapa
dc.contributor.referee3ID.fl_str_mv 04650816815
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/8371393564245194
dc.contributor.referee4.fl_str_mv MÃrcia Maria de Negreiros Pinto Rocha
dc.contributor.referee4ID.fl_str_mv 46546529300
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/2888374721836380
dc.contributor.authorID.fl_str_mv 47992506391
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9239964700549050
dc.contributor.author.fl_str_mv Silvana MagalhÃes Siqueira Menezes
contributor_str_mv Glauce Socorro de Barros Viana
Renata Ferreira de Carvalho LeitÃo
Ana Paula Negreiros Nunes Alves
AntÃnio Josà Lapa
MÃrcia Maria de Negreiros Pinto Rocha
dc.subject.cnpq.fl_str_mv FARMACOLOGIA
topic FARMACOLOGIA
dc.description.sponsorship.fl_txt_mv CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
dc.description.abstract.por.fl_txt_mv The immune/inflammatory response has a key role in the periodontal disease (DP) whose progression results from an imbalance between periodontopathogenic microorganisms and the host response. This leads to the production and release of inflammatory mediators and tissue damage. DP is considered the sixth complication in diabetes. Furthermore, diabetes mellitus and periodontitis present common links related to inflammation processes and immunologic system stimuli and, in the presence of diabetes with uncontrolled insulin levels, the aggravation of preexistant periodontitis may occur. Also, DP may reciprocally aggravate the diabetic state. Minocycline (M) is a second generation tetracycline showing anti-inflammatory effects independent of its antimicrobial action. The objectives of the present work were to investigate the effects of M (25 and 50 mg/kg, p.o.) in an experimental model of periodontal disease (DPE), in the presence and absence of alloxan-induced diabetes (DIA) in rats. DPE was induced through a nylon thread insertion and ligation in the second superior molar of male Wistar rats (200 g).For histological analyses and measurements of biochemical parameters, as glycemia, cholesterol, triglycerides and liver transaminases (ALT and AST) the groups (n=6) were divided : DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 and DPE+DIA+M50. After 11 or 30 days the animals were sacrificed. . Immunohitochemistry for TNF-α, iNOS and MMP-9 was performed in groups (n=4): DPE; DPE+DIA; DPE+M50; and DPE+DIA+M50. After 11 days the animals were sacrificed. The results showed that M50 presents a potent anti-inflammatory activity, preserving the alveolar and cement bones in the DPE and DPE+DIA models, after both periods of time. Under these experimental conditions, M50 also significantly reduced blood glucose levels. Furthermore, M50 reduced imunnostainings for TNF-α, iNOS and MMP-9. M25 did not significantly reduce the inflammatory process in DPE animals sacrificed at the 11th day after DPE induction.In addition, levels of triglycerides and total cholesterol were reduced in the DPE model, in the presence and absence of diabetes, after M25 and M50 treatments. Our data demonstrated that minocycline at both doses was well tolerated, and no significant alterations in ALT levels were observed in the DPE and DPE+DIA groups, at the 11th and 30th day, as well as on the levels of AST in groups DPE (11th day). However, the DPE + DIA group treated with M50 for 30 days presented a significant increase in AST levels. Our results strongly suggest that minocycline could be used for the periodontal disease treatment, since it protects the periodontium and reduces glycemia levels in the presence of the diabetic state. These beneficial effects are probably related to the potent anti-inflammatory properties of this drug, point out to its potential as an alternative for the treatment of diseases where the inflammatory process play a key role.
A resposta imune/inflamatÃria tem um papel fundamental na doenÃa periodontal (DP), onde a progressÃo à decorrente de um desequilÃbrio entre as bactÃrias periodontopatogÃnicas e a resposta do hospedeiro frente à agressÃo, com produÃÃo e liberaÃÃo de mediadores e subseqÃente dano tecidual. A DP à considerada a sexta complicaÃÃo clÃssica do diabetes. O diabetes mellitus e a periodontite possuem aspectos comuns no Ãmbito do estÃmulo inflamatÃrio e imunolÃgico, constituindo uma via de mÃo dupla, onde a primeira nÃo estando com sua taxa insulÃnica compensada poderà agravar uma periodontite preexistente e vice-versa. A minociclina(M) à uma tetraciclina de segunda geraÃÃo que apresenta efeitos anti-inflamatÃrios independentes de sua aÃÃo antimicrobiana. Os objetivos do presente estudo foram investigar os efeitos da M (25 e 50 mg/kg, via oral) em um modelo experimental de doenÃa periodontal (DPE), na presenÃa e ausÃncia de diabetes (DIA) induzida por aloxano em ratos. A DPE foi induzida passando-se um fio de nÃilon em torno do segundo molar superior esquerdo de ratos machos Wistar (200 g). Para as anÃlises histolÃgicas e determinaÃÃo dos parÃmetros bioquÃmicos, como glicemia, colesterol, triglicerÃdeos e enzimas hepÃticas (ALT e AST), os grupos (n=6) foram divididos em: DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 e DPE+DIA+M50. ApÃs 11 e 30 dias os animais foram sacrificados. A imunohistoquÃmica para TNF-α, iNOS e MMP-9 foi realizada nos grupos(n=4): DPE; DPE+DIA; DPE+M50 e DPE+DIA+M50. Os animais foram sacrificados apÃs 11 dias. Os resultados mostraram que a M50 apresenta potente atividade anti-inflamatÃria, preservando o osso alveolar e cemento, nos modelos experimentais de DPE e DPE + DIA, em ambos os perÃodos de estudo. Nestas mesmas condiÃÃes experimentais, a M50 tambÃm reduziu significantemente os nÃveis sanguÃneos de glicose. A M50 tambÃm reduziu a imunomarcaÃÃo para TNF-α, iNOS e MMP-9. A M25 nÃo reduziu o processo inflamatÃrio nos animais com DPE, sacrificados no 11 dia. Os nÃveis de triglicerÃdeos e colesterol total foram reduzidos nos modelos experimentais de DPE e de DPE + DIA, tratados com M25 e M50. Nossos resultados demonstraram que a minociclina em ambas as doses foi bem tolerada, sem alteraÃÃes significativas sobre os nÃveis de ALT, assim como sobre os nÃveis de AST nos grupos DPE (11 dia). Entretanto, o grupo DPE + DIA tratado com M50 por 30 dias, apresentou um aumento significativo na atividade da AST. Nossos resultados sugerem fortemente que a minociclina pode ser usada para o tratamento da doenÃa periodontal, tendo em vista que protege o periodonto e reduz nÃveis de glicemia na presenÃa do estado diabÃtico. Estes efeitos benÃficos sÃo provavelmente decorrentes das propriedades anti-inflamatÃrias desta droga, que surge como um potente tratamento alternativo para doenÃas onde o processo inflamatÃrio tem um papel fundamental.
description The immune/inflammatory response has a key role in the periodontal disease (DP) whose progression results from an imbalance between periodontopathogenic microorganisms and the host response. This leads to the production and release of inflammatory mediators and tissue damage. DP is considered the sixth complication in diabetes. Furthermore, diabetes mellitus and periodontitis present common links related to inflammation processes and immunologic system stimuli and, in the presence of diabetes with uncontrolled insulin levels, the aggravation of preexistant periodontitis may occur. Also, DP may reciprocally aggravate the diabetic state. Minocycline (M) is a second generation tetracycline showing anti-inflammatory effects independent of its antimicrobial action. The objectives of the present work were to investigate the effects of M (25 and 50 mg/kg, p.o.) in an experimental model of periodontal disease (DPE), in the presence and absence of alloxan-induced diabetes (DIA) in rats. DPE was induced through a nylon thread insertion and ligation in the second superior molar of male Wistar rats (200 g).For histological analyses and measurements of biochemical parameters, as glycemia, cholesterol, triglycerides and liver transaminases (ALT and AST) the groups (n=6) were divided : DPE; DPE+DIA; DPE+M25; DPE+M50; DPE+DIA+M25 and DPE+DIA+M50. After 11 or 30 days the animals were sacrificed. . Immunohitochemistry for TNF-α, iNOS and MMP-9 was performed in groups (n=4): DPE; DPE+DIA; DPE+M50; and DPE+DIA+M50. After 11 days the animals were sacrificed. The results showed that M50 presents a potent anti-inflammatory activity, preserving the alveolar and cement bones in the DPE and DPE+DIA models, after both periods of time. Under these experimental conditions, M50 also significantly reduced blood glucose levels. Furthermore, M50 reduced imunnostainings for TNF-α, iNOS and MMP-9. M25 did not significantly reduce the inflammatory process in DPE animals sacrificed at the 11th day after DPE induction.In addition, levels of triglycerides and total cholesterol were reduced in the DPE model, in the presence and absence of diabetes, after M25 and M50 treatments. Our data demonstrated that minocycline at both doses was well tolerated, and no significant alterations in ALT levels were observed in the DPE and DPE+DIA groups, at the 11th and 30th day, as well as on the levels of AST in groups DPE (11th day). However, the DPE + DIA group treated with M50 for 30 days presented a significant increase in AST levels. Our results strongly suggest that minocycline could be used for the periodontal disease treatment, since it protects the periodontium and reduces glycemia levels in the presence of the diabetic state. These beneficial effects are probably related to the potent anti-inflammatory properties of this drug, point out to its potential as an alternative for the treatment of diseases where the inflammatory process play a key role.
publishDate 2012
dc.date.issued.fl_str_mv 2012-06-22
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