Genotoxic effect of non-lethal concentrations of minocycline in human glial cell culture

Detalhes bibliográficos
Autor(a) principal: Puty, Bruna
Data de Publicação: 2020
Outros Autores: 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
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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spelling 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. 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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
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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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