Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4093 |
Resumo: | Minocycline has been proposed as a neuroprotective agent with pleiotropic effects on several experimental models of neurodegenerative diseases, including microglial inhibition. However, although most studies have focused on the central actions of minocycline in affecting microglial functions, other central nervous system (CNS) cell types may also be affected by this drug toxicity. Hence, considering that glial cells play a pivotal role on CNS physiology and are the main responsible for neuronal integrity, a comprehensive investigation on the effects of minocycline treatment on human glial cells is mandatory before translational studies to afford neuroprotection in humans. Therefore, we explored the cytotoxic and genotoxic effects of minocycline at different concentrations in glial cells using an in vitro model. To achieve this, U87 glial cell were exposed to 10–50 μg/mL for 24 h. After exposure, cell viability, general metabolic status and genotoxic assays were performed. No changes were observed in cell viability, however, the general metabolic status decreased over 20 μg/mL. In addition, although no chromossome aberrations were observed, evidences of genotoxicity, such as increase on micronucleus, buds and bridges, were observed from 10 μg/mL. These results suggest that minocycline may induce genotoxic effects even at concentrations considered previously safe and should be used with caution in translational studies. |
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Puty, BrunaNogueira, Iago César da CostaNogueira, Lygia SegaVasconcelos, Carolina PinheiroAraújo, Teka Mayara CorrêaBittencourt, Leonardo OliveiraFerreira, Railson de OliveiraOliveira, Edivaldo Herculano Correa deLeal, Walace GomesLima, Rafael Rodrigues2020-06-08T13:25:39Z2020-06-08T13:25:39Z2020PUTY, Bruna et al. Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture. Biomedicine & Pharmacotherapy, v. 128, n. 110285, 2020.1950-6007https://patua.iec.gov.br/handle/iec/409310.1016/j.biopha.2020.110285Minocycline has been proposed as a neuroprotective agent with pleiotropic effects on several experimental models of neurodegenerative diseases, including microglial inhibition. However, although most studies have focused on the central actions of minocycline in affecting microglial functions, other central nervous system (CNS) cell types may also be affected by this drug toxicity. Hence, considering that glial cells play a pivotal role on CNS physiology and are the main responsible for neuronal integrity, a comprehensive investigation on the effects of minocycline treatment on human glial cells is mandatory before translational studies to afford neuroprotection in humans. Therefore, we explored the cytotoxic and genotoxic effects of minocycline at different concentrations in glial cells using an in vitro model. To achieve this, U87 glial cell were exposed to 10–50 μg/mL for 24 h. After exposure, cell viability, general metabolic status and genotoxic assays were performed. No changes were observed in cell viability, however, the general metabolic status decreased over 20 μg/mL. In addition, although no chromossome aberrations were observed, evidences of genotoxicity, such as increase on micronucleus, buds and bridges, were observed from 10 μg/mL. These results suggest that minocycline may induce genotoxic effects even at concentrations considered previously safe and should be used with caution in translational studies.This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brazil (CAPES)–Finance Code 001 and supported by the Brazilian National Council for Scientific and Technological Development (CNPq).Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura Celular e Citogenética. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura Celular e Citogenética. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura Celular e Citogenética. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Experimental Neuroprotection and Neuroregeneration. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Science. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.engElsevierGenotoxic effect of non-lethal concentrations of minocycline in human glial cell cultureinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSistema Nervoso Central / anatomia & histologiaNeurogliaMinociclina / administração & dosagemMinociclina / toxicidadeDano ao DNA / genéticaCitotoxicidadeinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdfGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdfapplication/pdf1405836https://patua.iec.gov.br/bitstreams/bd002f06-0aa1-470a-ab94-fe0c57b1d79b/downloadde1fcda38d09c61bf9fa92f6d49c8a4eMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/f8e4280d-c49f-4b7c-807b-2ac3b6faf72f/download11832eea31b16df8613079d742d61793MD52TEXTGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdf.txtGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdf.txtExtracted texttext/plain41844https://patua.iec.gov.br/bitstreams/64709fc2-fe99-495c-aa6a-76a8984e7d27/downloada31e3586f913138f29fe219916318bc3MD55THUMBNAILGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdf.jpgGenotoxic effect of non-lethal concentrations of minocycline in human glial cell culture.pdf.jpgGenerated Thumbnailimage/jpeg5824https://patua.iec.gov.br/bitstreams/699c2a9a-5a52-46b5-bd11-ff22efff8e59/downloadf00c08ef5d201a8661731ab0f9df5284MD56iec/40932022-10-21 00:37:44.009oai:patua.iec.gov.br:iec/4093https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:37:44Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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 |
dc.title.pt_BR.fl_str_mv |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
title |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
spellingShingle |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture Puty, Bruna Sistema Nervoso Central / anatomia & histologia Neuroglia Minociclina / administração & dosagem Minociclina / toxicidade Dano ao DNA / genética Citotoxicidade |
title_short |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
title_full |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
title_fullStr |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
title_full_unstemmed |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
title_sort |
Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture |
author |
Puty, Bruna |
author_facet |
Puty, Bruna Nogueira, Iago César da Costa Nogueira, Lygia Sega Vasconcelos, Carolina Pinheiro Araújo, Teka Mayara Corrêa Bittencourt, Leonardo Oliveira Ferreira, Railson de Oliveira Oliveira, Edivaldo Herculano Correa de Leal, Walace Gomes Lima, Rafael Rodrigues |
author_role |
author |
author2 |
Nogueira, Iago César da Costa Nogueira, Lygia Sega Vasconcelos, Carolina Pinheiro Araújo, Teka Mayara Corrêa Bittencourt, Leonardo Oliveira Ferreira, Railson de Oliveira Oliveira, Edivaldo Herculano Correa de Leal, Walace Gomes Lima, Rafael Rodrigues |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Puty, Bruna Nogueira, Iago César da Costa Nogueira, Lygia Sega Vasconcelos, Carolina Pinheiro Araújo, Teka Mayara Corrêa Bittencourt, Leonardo Oliveira Ferreira, Railson de Oliveira Oliveira, Edivaldo Herculano Correa de Leal, Walace Gomes Lima, Rafael Rodrigues |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Sistema Nervoso Central / anatomia & histologia Neuroglia Minociclina / administração & dosagem Minociclina / toxicidade Dano ao DNA / genética Citotoxicidade |
topic |
Sistema Nervoso Central / anatomia & histologia Neuroglia Minociclina / administração & dosagem Minociclina / toxicidade Dano ao DNA / genética Citotoxicidade |
description |
Minocycline has been proposed as a neuroprotective agent with pleiotropic effects on several experimental models of neurodegenerative diseases, including microglial inhibition. However, although most studies have focused on the central actions of minocycline in affecting microglial functions, other central nervous system (CNS) cell types may also be affected by this drug toxicity. Hence, considering that glial cells play a pivotal role on CNS physiology and are the main responsible for neuronal integrity, a comprehensive investigation on the effects of minocycline treatment on human glial cells is mandatory before translational studies to afford neuroprotection in humans. Therefore, we explored the cytotoxic and genotoxic effects of minocycline at different concentrations in glial cells using an in vitro model. To achieve this, U87 glial cell were exposed to 10–50 μg/mL for 24 h. After exposure, cell viability, general metabolic status and genotoxic assays were performed. No changes were observed in cell viability, however, the general metabolic status decreased over 20 μg/mL. In addition, although no chromossome aberrations were observed, evidences of genotoxicity, such as increase on micronucleus, buds and bridges, were observed from 10 μg/mL. These results suggest that minocycline may induce genotoxic effects even at concentrations considered previously safe and should be used with caution in translational studies. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-06-08T13:25:39Z |
dc.date.available.fl_str_mv |
2020-06-08T13:25:39Z |
dc.date.issued.fl_str_mv |
2020 |
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.citation.fl_str_mv |
PUTY, Bruna et al. Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture. Biomedicine & Pharmacotherapy, v. 128, n. 110285, 2020. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4093 |
dc.identifier.issn.-.fl_str_mv |
1950-6007 |
dc.identifier.doi.-.fl_str_mv |
10.1016/j.biopha.2020.110285 |
identifier_str_mv |
PUTY, Bruna et al. Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture. Biomedicine & Pharmacotherapy, v. 128, n. 110285, 2020. 1950-6007 10.1016/j.biopha.2020.110285 |
url |
https://patua.iec.gov.br/handle/iec/4093 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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