Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica

Detalhes bibliográficos
Autor(a) principal: Lima, Stella Maris de Freitas
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UCB
Texto Completo: https://bdtd.ucb.br:8443/jspui/handle/tede/2474
Resumo: Failure of endodontic therapy is mainly based on the persistence of the microorganism inside the root canal system, perpetuating periradicular pathologies. The need for endodontic reintervention reduces the success rate and turns the development of new therapies into a necessity. Host defense peptides (HDPs) have a therapeutic potential because of its characteristics as broad spectrum antimicrobial activity, immunomodulatory capacity and repair induction. The present study aimed to demonstrate HDPs HHC-10, LL-37 and synoeca-MP activities compared to the commonly used chemical agents Ca(OH)2, NaOCl and chlorhexidine (CHX) in in vitro and in vivo environments. In vitro analysis involved (1) antimicrobial assays for MIC/MBC/MFC determination, antibiofilm and synergistic activities (against Candida albicans, Enterococcus faecalis and Staphylococcus aureus), (2) hemolytic assay and determination of therapeutic index, (3) immunomodulation assays (from RAW 264.7 monocytes) and (4) osteoclastogenesis assays (from mouse bone marrow cells). In vivo assays were based on periradicular lesions induced and treated in rats with subsequent analysis by radiographic, tomographic and histological examinations. Results demonstrated effective antimicrobial activity of HHC-10 (except antibiofilm activity) and synoeca-MP besides NaOCl and CHX. Higher therapeutic index was observed for peptides (HHC-10 and synoeca-MP) with low or no hemolytic activity. Synergism analysis demonstrated better interaction between synoeca-MP and CHX. Immune assays from monocyte cultures demonstrated a pro-inflammatory activity of LL-37 and synoeca-MP and a pro- and anti-inflammatory effect of HHC-10 and Ca(OH)2. However, none of the agents tested reduced osteoclastogenesis in vitro. In in vivo endodontic treatment conditions, HHC-10, synoeca-MP and Ca(OH)2 significantly reduced periapical lesions, although only peptides were able to reduce inflammation in histological analysis. Therefore, HHC-10 and synoeca-MP demonstrated in vitro and in vivo potential for application in endodontic therapy. However, further researches are needed regarding the mechanism of action of HDPs and the possible therapeutic formulations for future analysis in animal models.
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spelling Rezende, Taia Maria Bertohttp://lattes.cnpq.br/2108543063213963http://lattes.cnpq.br/5232734207402542Lima, Stella Maris de Freitas2018-11-07T17:53:52Z2018-08-21LIMA, Stella Maris de Freitas. Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica. 2018. 148 f. Tese (Programa Stricto Sensu em Ci??ncias Gen??micas e Biotecnologia) - Universidade Cat??lica de Bras??lia, Bras??lia, 2018.https://bdtd.ucb.br:8443/jspui/handle/tede/2474Failure of endodontic therapy is mainly based on the persistence of the microorganism inside the root canal system, perpetuating periradicular pathologies. The need for endodontic reintervention reduces the success rate and turns the development of new therapies into a necessity. Host defense peptides (HDPs) have a therapeutic potential because of its characteristics as broad spectrum antimicrobial activity, immunomodulatory capacity and repair induction. The present study aimed to demonstrate HDPs HHC-10, LL-37 and synoeca-MP activities compared to the commonly used chemical agents Ca(OH)2, NaOCl and chlorhexidine (CHX) in in vitro and in vivo environments. In vitro analysis involved (1) antimicrobial assays for MIC/MBC/MFC determination, antibiofilm and synergistic activities (against Candida albicans, Enterococcus faecalis and Staphylococcus aureus), (2) hemolytic assay and determination of therapeutic index, (3) immunomodulation assays (from RAW 264.7 monocytes) and (4) osteoclastogenesis assays (from mouse bone marrow cells). In vivo assays were based on periradicular lesions induced and treated in rats with subsequent analysis by radiographic, tomographic and histological examinations. Results demonstrated effective antimicrobial activity of HHC-10 (except antibiofilm activity) and synoeca-MP besides NaOCl and CHX. Higher therapeutic index was observed for peptides (HHC-10 and synoeca-MP) with low or no hemolytic activity. Synergism analysis demonstrated better interaction between synoeca-MP and CHX. Immune assays from monocyte cultures demonstrated a pro-inflammatory activity of LL-37 and synoeca-MP and a pro- and anti-inflammatory effect of HHC-10 and Ca(OH)2. However, none of the agents tested reduced osteoclastogenesis in vitro. In in vivo endodontic treatment conditions, HHC-10, synoeca-MP and Ca(OH)2 significantly reduced periapical lesions, although only peptides were able to reduce inflammation in histological analysis. Therefore, HHC-10 and synoeca-MP demonstrated in vitro and in vivo potential for application in endodontic therapy. However, further researches are needed regarding the mechanism of action of HDPs and the possible therapeutic formulations for future analysis in animal models.O insucesso da terapia endod??ntica est?? baseado na persist??ncia de microrganismos principalmente no interior do sistema de canais radiculares, perpetuando as patologias perirradiculares associadas ?? tal infec????o. A necessidade de reinterven????o endod??ntica reduz o percentual de sucesso e, portanto, o surgimento de novas terapias ?? necess??rio. Dessa forma, pept??deos de defesa do hospedeiro (PDHs) possuem potencial terap??utico associado ??s suas caracter??sticas de atividade antimicrobiana de amplo espectro, capacidade imunomodulat??ria e indu????o de reparo. O presente estudo objetivou demonstrar a atividade dos PDHs HHC-10, LL-37 e synoeca-MP comparado aos agentes qu??micos comumente utilizados Ca(OH)2, NaOCl e clorexidina (CHX) em ambientes in vitro e in vivo. Para tanto, foram realizadas an??lises in vitro envolvendo: (1) ensaios antimicrobianos com determina????o de MIC/MBC/MFC, atividade antibiofilme e atividade sin??rgica (contra Candida albicans, Enterococcus faecalis e Staphylococcus aureus), (2) ensaio hemol??tico e determina????o do ??ndice terap??utico, (3) ensaios de imunomodula????o (a partir de mon??citos RAW 264.7) e (4) ensaios osteoclastog??nese (a partir de c??lulas da medula ??ssea de camundongos). Os ensaios in vivo foram conduzidos a partir das les??es perirradiculares induzidas e tratadas em ratos com subsequente an??lise por exames radiogr??ficos, tomogr??ficos e histol??gicos. Assim, os resultados demonstraram efetiva atividade antimicrobiana dos pept??deos HHC-10 (exceto atividade antibiofilme) e synoeca-MP al??m do NaOCl e CHX. Observou-se maiores ??ndices terap??uticos para os pept??deos (HHC-10 e synoeca-MP) com baixa ou nenhuma atividade hemol??tica. As an??lises de intera????o demonstraram combina????o sin??rgica necessitando de menor concentra????o a partir da intera????o entre synoeca-MP e CHX. A partir da cultura de mon??citos, observou-se uma atividade pr??-inflamat??ria a partir dos pept??deos LL-37 e synoeca-MP e um efeito pr??- e anti-inflamat??rio do pept??deo HHC-10 e do Ca(OH)2. No entanto, nenhum dos agentes testados reduziram a osteoclastog??nese in vitro. J?? em condi????es de tratamento endod??ntico in vivo, os PDHs HHC-10, synoeca-MP e o Ca(OH)2 reduziram significativamente les??es periapicais, apesar de somente os pept??deos serem capazes de reduzir inflama????o em an??lises histol??gicas. Portanto, os pept??deos HHC-10 e synoeca-MP demonstraram potencial in vitro e in vivo para aplica????o na terapia endod??ntica. No entanto, faz-se necess??rio maiores investiga????es sobre o mecanismo de a????o dos mesmos e poss??veis formula????es terap??uticas para futuros testes em modelos animais.Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-07T17:53:28Z No. of bitstreams: 1 StellaMarisdeFreitasLimaTese2018.pdf: 12066835 bytes, checksum: 9ad384b4f040333154c3598b59852583 (MD5)Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-07T17:53:52Z (GMT) No. of bitstreams: 1 StellaMarisdeFreitasLimaTese2018.pdf: 12066835 bytes, checksum: 9ad384b4f040333154c3598b59852583 (MD5)Made available in DSpace on 2018-11-07T17:53:52Z (GMT). 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dc.title.por.fl_str_mv Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
title Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
spellingShingle Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
Lima, Stella Maris de Freitas
Endodontia
Medica????o intracanal
Pept??deos antimicrobianos
Pept??deos de defesa do hospedeiro
Host defense peptides
Antimicrobial peptides
Intracanal dressing
Endodontics
CNPQ::CIENCIAS BIOLOGICAS
title_short Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
title_full Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
title_fullStr Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
title_full_unstemmed Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
title_sort Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica
author Lima, Stella Maris de Freitas
author_facet Lima, Stella Maris de Freitas
author_role author
dc.contributor.advisor1.fl_str_mv Rezende, Taia Maria Berto
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2108543063213963
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5232734207402542
dc.contributor.author.fl_str_mv Lima, Stella Maris de Freitas
contributor_str_mv Rezende, Taia Maria Berto
dc.subject.por.fl_str_mv Endodontia
Medica????o intracanal
Pept??deos antimicrobianos
Pept??deos de defesa do hospedeiro
topic Endodontia
Medica????o intracanal
Pept??deos antimicrobianos
Pept??deos de defesa do hospedeiro
Host defense peptides
Antimicrobial peptides
Intracanal dressing
Endodontics
CNPQ::CIENCIAS BIOLOGICAS
dc.subject.eng.fl_str_mv Host defense peptides
Antimicrobial peptides
Intracanal dressing
Endodontics
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS
dc.description.abstract.eng.fl_txt_mv Failure of endodontic therapy is mainly based on the persistence of the microorganism inside the root canal system, perpetuating periradicular pathologies. The need for endodontic reintervention reduces the success rate and turns the development of new therapies into a necessity. Host defense peptides (HDPs) have a therapeutic potential because of its characteristics as broad spectrum antimicrobial activity, immunomodulatory capacity and repair induction. The present study aimed to demonstrate HDPs HHC-10, LL-37 and synoeca-MP activities compared to the commonly used chemical agents Ca(OH)2, NaOCl and chlorhexidine (CHX) in in vitro and in vivo environments. In vitro analysis involved (1) antimicrobial assays for MIC/MBC/MFC determination, antibiofilm and synergistic activities (against Candida albicans, Enterococcus faecalis and Staphylococcus aureus), (2) hemolytic assay and determination of therapeutic index, (3) immunomodulation assays (from RAW 264.7 monocytes) and (4) osteoclastogenesis assays (from mouse bone marrow cells). In vivo assays were based on periradicular lesions induced and treated in rats with subsequent analysis by radiographic, tomographic and histological examinations. Results demonstrated effective antimicrobial activity of HHC-10 (except antibiofilm activity) and synoeca-MP besides NaOCl and CHX. Higher therapeutic index was observed for peptides (HHC-10 and synoeca-MP) with low or no hemolytic activity. Synergism analysis demonstrated better interaction between synoeca-MP and CHX. Immune assays from monocyte cultures demonstrated a pro-inflammatory activity of LL-37 and synoeca-MP and a pro- and anti-inflammatory effect of HHC-10 and Ca(OH)2. However, none of the agents tested reduced osteoclastogenesis in vitro. In in vivo endodontic treatment conditions, HHC-10, synoeca-MP and Ca(OH)2 significantly reduced periapical lesions, although only peptides were able to reduce inflammation in histological analysis. Therefore, HHC-10 and synoeca-MP demonstrated in vitro and in vivo potential for application in endodontic therapy. However, further researches are needed regarding the mechanism of action of HDPs and the possible therapeutic formulations for future analysis in animal models.
dc.description.abstract.por.fl_txt_mv O insucesso da terapia endod??ntica est?? baseado na persist??ncia de microrganismos principalmente no interior do sistema de canais radiculares, perpetuando as patologias perirradiculares associadas ?? tal infec????o. A necessidade de reinterven????o endod??ntica reduz o percentual de sucesso e, portanto, o surgimento de novas terapias ?? necess??rio. Dessa forma, pept??deos de defesa do hospedeiro (PDHs) possuem potencial terap??utico associado ??s suas caracter??sticas de atividade antimicrobiana de amplo espectro, capacidade imunomodulat??ria e indu????o de reparo. O presente estudo objetivou demonstrar a atividade dos PDHs HHC-10, LL-37 e synoeca-MP comparado aos agentes qu??micos comumente utilizados Ca(OH)2, NaOCl e clorexidina (CHX) em ambientes in vitro e in vivo. Para tanto, foram realizadas an??lises in vitro envolvendo: (1) ensaios antimicrobianos com determina????o de MIC/MBC/MFC, atividade antibiofilme e atividade sin??rgica (contra Candida albicans, Enterococcus faecalis e Staphylococcus aureus), (2) ensaio hemol??tico e determina????o do ??ndice terap??utico, (3) ensaios de imunomodula????o (a partir de mon??citos RAW 264.7) e (4) ensaios osteoclastog??nese (a partir de c??lulas da medula ??ssea de camundongos). Os ensaios in vivo foram conduzidos a partir das les??es perirradiculares induzidas e tratadas em ratos com subsequente an??lise por exames radiogr??ficos, tomogr??ficos e histol??gicos. Assim, os resultados demonstraram efetiva atividade antimicrobiana dos pept??deos HHC-10 (exceto atividade antibiofilme) e synoeca-MP al??m do NaOCl e CHX. Observou-se maiores ??ndices terap??uticos para os pept??deos (HHC-10 e synoeca-MP) com baixa ou nenhuma atividade hemol??tica. As an??lises de intera????o demonstraram combina????o sin??rgica necessitando de menor concentra????o a partir da intera????o entre synoeca-MP e CHX. A partir da cultura de mon??citos, observou-se uma atividade pr??-inflamat??ria a partir dos pept??deos LL-37 e synoeca-MP e um efeito pr??- e anti-inflamat??rio do pept??deo HHC-10 e do Ca(OH)2. No entanto, nenhum dos agentes testados reduziram a osteoclastog??nese in vitro. J?? em condi????es de tratamento endod??ntico in vivo, os PDHs HHC-10, synoeca-MP e o Ca(OH)2 reduziram significativamente les??es periapicais, apesar de somente os pept??deos serem capazes de reduzir inflama????o em an??lises histol??gicas. Portanto, os pept??deos HHC-10 e synoeca-MP demonstraram potencial in vitro e in vivo para aplica????o na terapia endod??ntica. No entanto, faz-se necess??rio maiores investiga????es sobre o mecanismo de a????o dos mesmos e poss??veis formula????es terap??uticas para futuros testes em modelos animais.
description Failure of endodontic therapy is mainly based on the persistence of the microorganism inside the root canal system, perpetuating periradicular pathologies. The need for endodontic reintervention reduces the success rate and turns the development of new therapies into a necessity. Host defense peptides (HDPs) have a therapeutic potential because of its characteristics as broad spectrum antimicrobial activity, immunomodulatory capacity and repair induction. The present study aimed to demonstrate HDPs HHC-10, LL-37 and synoeca-MP activities compared to the commonly used chemical agents Ca(OH)2, NaOCl and chlorhexidine (CHX) in in vitro and in vivo environments. In vitro analysis involved (1) antimicrobial assays for MIC/MBC/MFC determination, antibiofilm and synergistic activities (against Candida albicans, Enterococcus faecalis and Staphylococcus aureus), (2) hemolytic assay and determination of therapeutic index, (3) immunomodulation assays (from RAW 264.7 monocytes) and (4) osteoclastogenesis assays (from mouse bone marrow cells). In vivo assays were based on periradicular lesions induced and treated in rats with subsequent analysis by radiographic, tomographic and histological examinations. Results demonstrated effective antimicrobial activity of HHC-10 (except antibiofilm activity) and synoeca-MP besides NaOCl and CHX. Higher therapeutic index was observed for peptides (HHC-10 and synoeca-MP) with low or no hemolytic activity. Synergism analysis demonstrated better interaction between synoeca-MP and CHX. Immune assays from monocyte cultures demonstrated a pro-inflammatory activity of LL-37 and synoeca-MP and a pro- and anti-inflammatory effect of HHC-10 and Ca(OH)2. However, none of the agents tested reduced osteoclastogenesis in vitro. In in vivo endodontic treatment conditions, HHC-10, synoeca-MP and Ca(OH)2 significantly reduced periapical lesions, although only peptides were able to reduce inflammation in histological analysis. Therefore, HHC-10 and synoeca-MP demonstrated in vitro and in vivo potential for application in endodontic therapy. However, further researches are needed regarding the mechanism of action of HDPs and the possible therapeutic formulations for future analysis in animal models.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-11-07T17:53:52Z
dc.date.issued.fl_str_mv 2018-08-21
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
status_str publishedVersion
format doctoralThesis
dc.identifier.citation.fl_str_mv LIMA, Stella Maris de Freitas. Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica. 2018. 148 f. Tese (Programa Stricto Sensu em Ci??ncias Gen??micas e Biotecnologia) - Universidade Cat??lica de Bras??lia, Bras??lia, 2018.
dc.identifier.uri.fl_str_mv https://bdtd.ucb.br:8443/jspui/handle/tede/2474
identifier_str_mv LIMA, Stella Maris de Freitas. Pept??deos de defesa do hospedeiro como adjuvantes na terapia endod??ntica. 2018. 148 f. Tese (Programa Stricto Sensu em Ci??ncias Gen??micas e Biotecnologia) - Universidade Cat??lica de Bras??lia, Bras??lia, 2018.
url https://bdtd.ucb.br:8443/jspui/handle/tede/2474
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Cat??lica de Bras??lia
dc.publisher.program.fl_str_mv Programa Stricto Sensu em Ci??ncias Gen??micas e Biotecnologia
dc.publisher.initials.fl_str_mv UCB
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Escola de Sa??de e Medicina
publisher.none.fl_str_mv Universidade Cat??lica de Bras??lia
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UCB
instname:Universidade Católica de Brasília (UCB)
instacron:UCB
instname_str Universidade Católica de Brasília (UCB)
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