Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática

Detalhes bibliográficos
Autor(a) principal: Malta, Cristiana Pereira
Data de Publicação: 2022
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
dARK ID: ark:/26339/001300000bg3p
Texto Completo: http://repositorio.ufsm.br/handle/1/27791
Resumo: This thesis presented three objectives to characterize the biocompatibility of endodontic sealers: (1) to evaluate, through the Artemia salina lethality test, the toxicity of a novel calcium silicatebased root canal sealer (Bio-C Sealer) in comparison to Endosequence BC Sealer and AH Plus; (2) to determine in silico toxicity predictions of test compounds from Endosequence BC Sealer and AH Plus and perform a computational simulation via molecular docking of the interaction between these substances and mediators of periapical inflammation; (3) to compare histocompatibility, cytotoxicity and genotoxicity of premixed calcium silicate-based root canal sealers, with the AH Plus, systematically reviewing in vivo animal and in vitro laboratory studies. In the first study, the lethality test determined the larval survival rate and acute toxicity (LC50). Data were analyzed using ANOVA, Newman-Keuls and Dunett tests, with a significance level of 5%. Bio-C Sealer and Endosequence BC Sealer showed lower toxicity than AH Plus and the latter had the lowest LC50. In the second study, chemical information of the test compounds was obtained from the PubChem site and predictions were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the program Autodock4 AMDock v.1.5.2 to analyze interactions between different proteins present in the periapical inflammatory process (IL-1β, IL-6, IL-8, IL-10 and TNF-α) and ligands present in the sealers (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate). Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favorable docking, however bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. The third study followed the PRISMA guidelines and electronic searches were performed in PubMed/MEDLINE and EMBASE. Inclusion criteria encompassed in vivo animal and in vitro laboratory studies that evaluated histocompatibility, cytotoxicity and/or genotoxicity of premixed calcium silicatebased root canal sealers compared to AH Plus. Meta-analysis was performed using Stata program and random effect model. Fifty-two studies were included for data extraction and 14 in the meta-analysis. The premixed calcium silicate-based sealers showed better histocompatibility at 30 days and greater cell viability of undiluted extracts at 72 hours and extracts with 1:2 and 1:4 dilutions at 24 and 72 hours. However, there was no difference between materials for genotoxicity. According to the results, it can be concluded that premixed calcium silicate-based root canal sealers have a biological behavior superior to the “gold standard” AH Plus.
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spelling Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemáticaBiocompatibility of calcium silicate-based and epoxy resinbased root canal sealers: in vitro and in silico studies and systematic reviewMateriais obturadores do canal radicularToxicidadeArtemiaDocking molecularRevisão sistemáticaRoot canal filling materialsToxicityMolecular dockingSystematic reviewCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIAThis thesis presented three objectives to characterize the biocompatibility of endodontic sealers: (1) to evaluate, through the Artemia salina lethality test, the toxicity of a novel calcium silicatebased root canal sealer (Bio-C Sealer) in comparison to Endosequence BC Sealer and AH Plus; (2) to determine in silico toxicity predictions of test compounds from Endosequence BC Sealer and AH Plus and perform a computational simulation via molecular docking of the interaction between these substances and mediators of periapical inflammation; (3) to compare histocompatibility, cytotoxicity and genotoxicity of premixed calcium silicate-based root canal sealers, with the AH Plus, systematically reviewing in vivo animal and in vitro laboratory studies. In the first study, the lethality test determined the larval survival rate and acute toxicity (LC50). Data were analyzed using ANOVA, Newman-Keuls and Dunett tests, with a significance level of 5%. Bio-C Sealer and Endosequence BC Sealer showed lower toxicity than AH Plus and the latter had the lowest LC50. In the second study, chemical information of the test compounds was obtained from the PubChem site and predictions were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the program Autodock4 AMDock v.1.5.2 to analyze interactions between different proteins present in the periapical inflammatory process (IL-1β, IL-6, IL-8, IL-10 and TNF-α) and ligands present in the sealers (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate). Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favorable docking, however bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. The third study followed the PRISMA guidelines and electronic searches were performed in PubMed/MEDLINE and EMBASE. Inclusion criteria encompassed in vivo animal and in vitro laboratory studies that evaluated histocompatibility, cytotoxicity and/or genotoxicity of premixed calcium silicatebased root canal sealers compared to AH Plus. Meta-analysis was performed using Stata program and random effect model. Fifty-two studies were included for data extraction and 14 in the meta-analysis. The premixed calcium silicate-based sealers showed better histocompatibility at 30 days and greater cell viability of undiluted extracts at 72 hours and extracts with 1:2 and 1:4 dilutions at 24 and 72 hours. However, there was no difference between materials for genotoxicity. According to the results, it can be concluded that premixed calcium silicate-based root canal sealers have a biological behavior superior to the “gold standard” AH Plus.Esta tese apresentou três objetivos para caracterizar a biocompatibilidade de cimentos endodônticos: (1) avaliar, por meio do ensaio de letalidade de Artemia salina, a toxicidade de um novo cimento endodôntico à base de silicato de cálcio (Bio-C Sealer), em comparação com Endosequence BC Sealer e AH Plus; (2) verificar previsões de toxicidade in silico dos compostos-teste do Endosequence BC Sealer e AH Plus e simular computacionalmente, via docking molecular, a interação dessas substâncias com mediadores da inflamação periapical; (3) comparar histocompatibilidade, citotoxicidade e genotoxicidade dos cimentos endodônticos pré-misturados à base de silicato de cálcio, com o AH Plus, revisando sistematicamente estudos em animais in vivo e laboratoriais in vitro. No primeiro estudo, o teste de letalidade determinou a taxa de sobrevivência das larvas e a toxicidade aguda (LC50). Os dados foram analisados pelos testes ANOVA, Newman-Keuls e Dunett, com nível de significância de 5%. Bio-C Sealer e Endosequence BC Sealer apresentaram menor toxicidade que o AH Plus e este teve o valor mais baixo de LC50. No segundo estudo, as informações químicas dos compostos-teste foram obtidas no site PubChem e as predições foram determinadas pelas plataformas Molinspiration Cheminformatics, pkCSM, ProTox-II e OSIRIS Property Explorer. O docking molecular foi realizado no programa Autodock4 AMDock v.1.5.2 para verificar as interações entre diferentes proteínas presentes no processo inflamatório periapical (IL-1β, IL-6, IL-8, IL-10 e TNF-α) e ligantes presentes nos cimentos (silicato de cálcio hidratado, óxido de zircônio, resina epóxi bisfenol-A, dibenzilamina, óxido de ferro e tungstato de cálcio). A resina epóxi bisfenol-A apresentou a menor dose máxima tolerada em humanos e foi o composto-teste com maior número de propriedades toxicológicas positivas (hepatotoxicidade, carcinogenicidade e irritante). Todos os sistemas apresentaram docking favorável, mas resina epóxi bisfenol-A e dibenzilamina foram os ligantes com maior afinidade com as citocinas testadas. O terceiro estudo seguiu as diretrizes PRISMA e as buscas eletrônicas foram realizadas nas bases PubMed/MEDLINE e EMBASE. Os critérios de inclusão englobaram estudos em animais in vivo e laboratoriais in vitro que avaliaram histocompatibilidade, citotoxicidade e/ou genotoxicidade de cimentos endodônticos pré-misturados à base de silicato de cálcio em comparação com o AH Plus. A metanálise foi realizada no programa Stata utilizando modelo de efeito aleatório. Foram incluídos 52 estudos na extração de dados e 14 na metanálise. Os cimentos pré-misturados à base de silicato de cálcio apresentaram melhor histocompatibilidade aos 30 dias e maior viabilidade celular dos extratos não diluídos em 72 horas e com diluição 1:2 e 1:4 em 24 e 72 horas. Porém, não houve diferença entre os materiais para genotoxicidade. De acordo com os resultados, conclui-se que cimentos endodônticos pré-misturados à base de silicato de cálcio possuem comportamento biológico superior ao “padrão-ouro” AH Plus.Universidade Federal de Santa MariaBrasilOdontologiaUFSMPrograma de Pós-Graduação em Ciências OdontológicasCentro de Ciências da SaúdeMorgental, Renata Dornelleshttp://lattes.cnpq.br/3833226179501044Bier, Carlos Alexandre SouzaLima, Carolina Oliveira dePappen, Fernanda GeraldoMóra, Patrícia Maria Poli KopperMartelo, Roberta BossoMalta, Cristiana Pereira2023-02-14T11:14:37Z2023-02-14T11:14:37Z2022-12-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/27791ark:/26339/001300000bg3pporAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-02-14T11:14:37Zoai:repositorio.ufsm.br:1/27791Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-02-14T11:14:37Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
Biocompatibility of calcium silicate-based and epoxy resinbased root canal sealers: in vitro and in silico studies and systematic review
title Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
spellingShingle Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
Malta, Cristiana Pereira
Materiais obturadores do canal radicular
Toxicidade
Artemia
Docking molecular
Revisão sistemática
Root canal filling materials
Toxicity
Molecular docking
Systematic review
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
title_short Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
title_full Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
title_fullStr Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
title_full_unstemmed Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
title_sort Biocompatibilidade de cimentos endodônticos à base de silicato de cálcio e resina epóxi: estudos in vitro, in silico e revisão sistemática
author Malta, Cristiana Pereira
author_facet Malta, Cristiana Pereira
author_role author
dc.contributor.none.fl_str_mv Morgental, Renata Dornelles
http://lattes.cnpq.br/3833226179501044
Bier, Carlos Alexandre Souza
Lima, Carolina Oliveira de
Pappen, Fernanda Geraldo
Móra, Patrícia Maria Poli Kopper
Martelo, Roberta Bosso
dc.contributor.author.fl_str_mv Malta, Cristiana Pereira
dc.subject.por.fl_str_mv Materiais obturadores do canal radicular
Toxicidade
Artemia
Docking molecular
Revisão sistemática
Root canal filling materials
Toxicity
Molecular docking
Systematic review
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
topic Materiais obturadores do canal radicular
Toxicidade
Artemia
Docking molecular
Revisão sistemática
Root canal filling materials
Toxicity
Molecular docking
Systematic review
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
description This thesis presented three objectives to characterize the biocompatibility of endodontic sealers: (1) to evaluate, through the Artemia salina lethality test, the toxicity of a novel calcium silicatebased root canal sealer (Bio-C Sealer) in comparison to Endosequence BC Sealer and AH Plus; (2) to determine in silico toxicity predictions of test compounds from Endosequence BC Sealer and AH Plus and perform a computational simulation via molecular docking of the interaction between these substances and mediators of periapical inflammation; (3) to compare histocompatibility, cytotoxicity and genotoxicity of premixed calcium silicate-based root canal sealers, with the AH Plus, systematically reviewing in vivo animal and in vitro laboratory studies. In the first study, the lethality test determined the larval survival rate and acute toxicity (LC50). Data were analyzed using ANOVA, Newman-Keuls and Dunett tests, with a significance level of 5%. Bio-C Sealer and Endosequence BC Sealer showed lower toxicity than AH Plus and the latter had the lowest LC50. In the second study, chemical information of the test compounds was obtained from the PubChem site and predictions were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the program Autodock4 AMDock v.1.5.2 to analyze interactions between different proteins present in the periapical inflammatory process (IL-1β, IL-6, IL-8, IL-10 and TNF-α) and ligands present in the sealers (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate). Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favorable docking, however bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. The third study followed the PRISMA guidelines and electronic searches were performed in PubMed/MEDLINE and EMBASE. Inclusion criteria encompassed in vivo animal and in vitro laboratory studies that evaluated histocompatibility, cytotoxicity and/or genotoxicity of premixed calcium silicatebased root canal sealers compared to AH Plus. Meta-analysis was performed using Stata program and random effect model. Fifty-two studies were included for data extraction and 14 in the meta-analysis. The premixed calcium silicate-based sealers showed better histocompatibility at 30 days and greater cell viability of undiluted extracts at 72 hours and extracts with 1:2 and 1:4 dilutions at 24 and 72 hours. However, there was no difference between materials for genotoxicity. According to the results, it can be concluded that premixed calcium silicate-based root canal sealers have a biological behavior superior to the “gold standard” AH Plus.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-12
2023-02-14T11:14:37Z
2023-02-14T11:14:37Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/27791
dc.identifier.dark.fl_str_mv ark:/26339/001300000bg3p
url http://repositorio.ufsm.br/handle/1/27791
identifier_str_mv ark:/26339/001300000bg3p
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Odontologia
UFSM
Programa de Pós-Graduação em Ciências Odontológicas
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Odontologia
UFSM
Programa de Pós-Graduação em Ciências Odontológicas
Centro de Ciências da Saúde
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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