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

[Display omitted] •Different minocycline concentration are not related to cell death on U87 glial-like cell.•Decreased cell general metabolism status up to 20 μg/mL.•Chromosomal instability as micronucleus, buds and bridges are induced up to 10 μg/mL.•Minocycline has genotoxic effect on U87 glial-li...

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Published in:	Biomedicine & pharmacotherapy Vol. 128; p. 110285
Main Authors:	Puty, Bruna, Nogueira, Iago César da Costa, Nogueira, Lygia S., Vasconcelos, Carolina Pinheiro, Araújo, Teka Mayara Corrêa, Bittencourt, Leonardo Oliveira, Ferreira, Railson de Oliveira, Oliveira, Edivaldo Herculano C. de, Leal, Walace Gomes, Lima, Rafael Rodrigues
Format:	Journal Article
Language:	English
Published:	France Elsevier Masson SAS 01-08-2020 Elsevier
Subjects:	Cell Line Cell Survival - drug effects Chromosome Aberrations - chemically induced Comet Assay Cytotoxicity DNA Damage Dose-Response Relationship, Drug Glia Humans Micronuclei, Chromosome-Defective - chemically induced Micronucleus Tests Minocycline Minocycline - toxicity Neuroglia - drug effects Neuroglia - metabolism Neuroglia - pathology Neuroprotective Agents - toxicity Risk Assessment Minocycline Cytotoxicity Glia DNA damage
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Summary:	[Display omitted] •Different minocycline concentration are not related to cell death on U87 glial-like cell.•Decreased cell general metabolism status up to 20 μg/mL.•Chromosomal instability as micronucleus, buds and bridges are induced up to 10 μg/mL.•Minocycline has genotoxic effect on U87 glial-like cells after 24 h. 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.
ISSN:	0753-3322 1950-6007
DOI:	10.1016/j.biopha.2020.110285