Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1590/0103-6440201302229 http://hdl.handle.net/11449/126179 |
Resumo: | Bisphosphonate-induced osteonecrosis has been related to the cytotoxicity of these drugs on oral mucosa cells. A previous study showed that 5 µM of zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is the highest concentration of this drug found in the oral cavity of patients under treatment. Therefore, in order to simulate an osteonecrosis clinical condition, the aim of this study was to evaluate the highest concentration of ZA applied on human epithelial cells (HaCaT) and gingival fibroblasts. For this purpose, cells (3×104 cells/cm2) were seeded in wells for 48 h using complete culture medium (cDMEM). After 48 h incubation, the cDMEM was replaced by fresh serum-free culture medium (DMEM-FBS) in which the cells were maintained for additional 24 h. Then, 5 µM ZA were added to the DMEM–FBS and the cells incubated in contact with the drug for 48 h. After this period, the number of viable cells (trypan blue), cell viability (MTT assay), total protein (TP) production and cell morphology (SEM analysis) were assessed. Data were analyzed statistically by Mann-Whitney, ANOVA and Tukey's test (α=0.05). ZA caused a significant reduction in the number of viable cells and decreased the metabolic activity of both cell lines. However, decrease of TP production occurred only in the epithelial cell cultures. Morphological alterations were observed in both cell types treated with ZA. In conclusion, ZA (5 µM) was cytotoxic to human epithelial cells and gingival fibroblast cultures, which could be associated, clinically, with the development of bisphosphonate-induced osteonecrosis. |
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Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblastsbisphosphonatescytotoxicityepithelial cellsfibroblastsBisphosphonate-induced osteonecrosis has been related to the cytotoxicity of these drugs on oral mucosa cells. A previous study showed that 5 µM of zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is the highest concentration of this drug found in the oral cavity of patients under treatment. Therefore, in order to simulate an osteonecrosis clinical condition, the aim of this study was to evaluate the highest concentration of ZA applied on human epithelial cells (HaCaT) and gingival fibroblasts. For this purpose, cells (3×104 cells/cm2) were seeded in wells for 48 h using complete culture medium (cDMEM). After 48 h incubation, the cDMEM was replaced by fresh serum-free culture medium (DMEM-FBS) in which the cells were maintained for additional 24 h. Then, 5 µM ZA were added to the DMEM–FBS and the cells incubated in contact with the drug for 48 h. After this period, the number of viable cells (trypan blue), cell viability (MTT assay), total protein (TP) production and cell morphology (SEM analysis) were assessed. Data were analyzed statistically by Mann-Whitney, ANOVA and Tukey's test (α=0.05). ZA caused a significant reduction in the number of viable cells and decreased the metabolic activity of both cell lines. However, decrease of TP production occurred only in the epithelial cell cultures. Morphological alterations were observed in both cell types treated with ZA. In conclusion, ZA (5 µM) was cytotoxic to human epithelial cells and gingival fibroblast cultures, which could be associated, clinically, with the development of bisphosphonate-induced osteonecrosis.A osteonecrose induzida por bisfosfonatos tem sido associada a um efeito citotóxico destes medicamentos sobre as células da mucosa oral. Um estudo recente demonstrou que 5 µM de ácido zoledrônico (AZ), um potente bisfosfonato nitrogenado, foi a maior concentração encontrada na cavidade oral da pacientes em tratamento com este medicamento. Portanto, para simular esta condição in vivo, o objetivo deste estudo foi avaliar o efeito da aplicação desta concentração de AZ sobre células epiteliais (HaCaT) e fibroblasto de gengiva. As células foram semeadas (3×104 células/cm2) e incubadas por 48 h em placas de 24 compartimentos, utilizando meio de cultura completo (cDMEM). Após permanecer por 24 h em DMEM sem soro fetal bovino (DMEM-SFB), 5 µM do AZ foram adicionados a este meio de cultura, o qual foi incubado em contato com as células por 48 h. Após este período, foram avaliados o número de células viáveis (trypan blue), viabilidade celular (teste de MTT), produção de proteína total e a morfologia celular (MEV). Os dados obtidos foram submetidos aos testes estatísticos de Mann-Whitney e ANOVA complementada por testes de Tukey (p>0,05). Foi demonstrado que o AZ causou diminuição significativa no número de células viáveis, além de redução do metabolismo celular para ambos os tipos celulares avaliados. Porém, redução na produção de proteína total ocorreu apenas para as células epiteliais. Alterações morfológicas foram observadas em ambos os tipos celulares tratados com AZ. Estes dados científicos indicam que a concentração de AZ avaliada neste estudo (5 µM) apresenta ação citotóxica sobre células epiteliais e fibroblastos de gengiva, o que poderia estar associado, clinicamente, ao desenvolvimento da osteonecrose induzida por bisfosfonatos.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Piracicaba School of Dentistry UNICAMP University of CampinasAraraquara School of Dentistry UNESP - Univ Estadual PaulistaButantan Institute/Departament of Morphology of UNIFESP - Federal University of Sao Paulo Laboratory of GeneticsAraraquara School of Dentistry UNESP - Univ Estadual PaulistaFundação Odontológica de Ribeirão PretoUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Basso, Fernanda GoncalvesPansani, Taisa NogueiraOliveira, Camila Favero DeTurrioni, Ana Paula SilveiraSoares, Diana GabrielaHebling, JosimeriCosta, Carlos Alberto De Souza2015-08-06T16:14:44Z2015-08-06T16:14:44Z2013-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article551-558application/pdfhttp://dx.doi.org/10.1590/0103-6440201302229Brazilian Dental Journal. Fundação Odontológica de Ribeirão Preto, v. 24, n. 6, p. 551-558, 2013.0103-6440http://hdl.handle.net/11449/12617910.1590/0103-6440201302229S0103-64402013000600551S0103-64402013000600551.pdfSciELOreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Dental Journal0,476info:eu-repo/semantics/openAccess2023-12-24T06:19:23Zoai:repositorio.unesp.br:11449/126179Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:10:52.070287Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
title |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
spellingShingle |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts Basso, Fernanda Goncalves bisphosphonates cytotoxicity epithelial cells fibroblasts |
title_short |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
title_full |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
title_fullStr |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
title_full_unstemmed |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
title_sort |
Cytotoxic Effects of Zoledronic Acid on Human Epithelial Cells and Gingival Fibroblasts |
author |
Basso, Fernanda Goncalves |
author_facet |
Basso, Fernanda Goncalves Pansani, Taisa Nogueira Oliveira, Camila Favero De Turrioni, Ana Paula Silveira Soares, Diana Gabriela Hebling, Josimeri Costa, Carlos Alberto De Souza |
author_role |
author |
author2 |
Pansani, Taisa Nogueira Oliveira, Camila Favero De Turrioni, Ana Paula Silveira Soares, Diana Gabriela Hebling, Josimeri Costa, Carlos Alberto De Souza |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Basso, Fernanda Goncalves Pansani, Taisa Nogueira Oliveira, Camila Favero De Turrioni, Ana Paula Silveira Soares, Diana Gabriela Hebling, Josimeri Costa, Carlos Alberto De Souza |
dc.subject.por.fl_str_mv |
bisphosphonates cytotoxicity epithelial cells fibroblasts |
topic |
bisphosphonates cytotoxicity epithelial cells fibroblasts |
description |
Bisphosphonate-induced osteonecrosis has been related to the cytotoxicity of these drugs on oral mucosa cells. A previous study showed that 5 µM of zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is the highest concentration of this drug found in the oral cavity of patients under treatment. Therefore, in order to simulate an osteonecrosis clinical condition, the aim of this study was to evaluate the highest concentration of ZA applied on human epithelial cells (HaCaT) and gingival fibroblasts. For this purpose, cells (3×104 cells/cm2) were seeded in wells for 48 h using complete culture medium (cDMEM). After 48 h incubation, the cDMEM was replaced by fresh serum-free culture medium (DMEM-FBS) in which the cells were maintained for additional 24 h. Then, 5 µM ZA were added to the DMEM–FBS and the cells incubated in contact with the drug for 48 h. After this period, the number of viable cells (trypan blue), cell viability (MTT assay), total protein (TP) production and cell morphology (SEM analysis) were assessed. Data were analyzed statistically by Mann-Whitney, ANOVA and Tukey's test (α=0.05). ZA caused a significant reduction in the number of viable cells and decreased the metabolic activity of both cell lines. However, decrease of TP production occurred only in the epithelial cell cultures. Morphological alterations were observed in both cell types treated with ZA. In conclusion, ZA (5 µM) was cytotoxic to human epithelial cells and gingival fibroblast cultures, which could be associated, clinically, with the development of bisphosphonate-induced osteonecrosis. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-12-01 2015-08-06T16:14:44Z 2015-08-06T16:14:44Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/0103-6440201302229 Brazilian Dental Journal. Fundação Odontológica de Ribeirão Preto, v. 24, n. 6, p. 551-558, 2013. 0103-6440 http://hdl.handle.net/11449/126179 10.1590/0103-6440201302229 S0103-64402013000600551 S0103-64402013000600551.pdf |
url |
http://dx.doi.org/10.1590/0103-6440201302229 http://hdl.handle.net/11449/126179 |
identifier_str_mv |
Brazilian Dental Journal. Fundação Odontológica de Ribeirão Preto, v. 24, n. 6, p. 551-558, 2013. 0103-6440 10.1590/0103-6440201302229 S0103-64402013000600551 S0103-64402013000600551.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brazilian Dental Journal 0,476 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
551-558 application/pdf |
dc.publisher.none.fl_str_mv |
Fundação Odontológica de Ribeirão Preto |
publisher.none.fl_str_mv |
Fundação Odontológica de Ribeirão Preto |
dc.source.none.fl_str_mv |
SciELO reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129294842462208 |