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In vitro neurotoxicity evaluation of piperazine designer drugs in differentiated human neuroblastoma SH-SY5Y cells

2015-04-20Journal article Unknown
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dc.contributor.authorArbo, M.D.
dc.contributor.authorSilva, R.
dc.contributor.authorBarbosa, D.J.
dc.contributor.authorda Silva, D. Dias
dc.contributor.authorSilva, S.P.
dc.contributor.authorTeixeira, João Paulo
dc.contributor.authorBastos, M.L.
dc.contributor.authorCarmo, H.
dc.date.accessioned2016-02-16T17:18:45Z
dc.date.available2018-01-01T01:30:09Z
dc.date.issued2015-04-20
dc.description.abstractAbuse of synthetic drugs is widespread worldwide. Studies indicate that piperazine designer drugs act as substrates at dopaminergic and serotonergic receptors and/or transporters in the brain. This work aimed to investigate the cytotoxicity of N-benzylpiperazine, 1-(3-trifluoromethylphenyl)piperazine, 1-(4-methoxyphenyl)piperazine and 1-(3,4-methylenedioxybenzyl)piperazine in the differentiated human neuroblastoma SH-SY5Y cell line. Cytotoxicity was evaluated after 24 h incubations through the MTT reduction and neutral red uptake assays. Oxidative stress (reactive oxygen and nitrogen species production and glutathione content) and energetic (ATP content) parameters, as well as intracellular Ca(2+) , mitochondrial membrane potential, DNA damage (comet assay) and cell death mode were also evaluated. Complete cytotoxicity curves were obtained after 24 h incubations with each drug. A significant decrease in intracellular total glutathione content was noted for all the tested drugs. All drugs caused a significant increase of intracellular free Ca(2+) levels, accompanied by mitochondrial hyperpolarization. However, ATP levels remained unchanged. The investigation of cell death mode revealed a predominance of early apoptotic cells. No genotoxicity was found in the comet assay. Among the tested drugs, 1-(3-trifluoromethylphenyl)piperazine was the most cytotoxic. Overall, piperazine designer drugs are potentially neurotoxic, supporting concerns on risks associated with the abuse of these drugs. Copyright © 2015 John Wiley & Sons, Ltd.pt_PT
dc.description.sponsorshipMarcelo Dutra Arbo is the recipient of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES Foundation – Brazil) fellowship (Proc. BEX 0593/10-9). Renata Silva and Daniel José Barbosa were supported by fellowships (SFRH/BD/29559/2006 and SFRH/BD/64939/2009, respectively) from Fundação para a Ciência e Tecnologia (FCT), Portugal. This work was supported by the European Union (FEDER funds through COMPETE – Operational Programme for Competitiveness Factors) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through the project Pest-C/EQB/LA0006/2013. The work also received financial support from the European Union (FEDER funds under the framework of QREN through Project NORTE-07-0124-FEDER-000067.pt_PT
dc.identifier.citationJ Appl Toxicol. 2016 Jan;36(1):121-30. doi: 10.1002/jat.3153. Epub 2015 Apr 20.pt_PT
dc.identifier.doi10.1002/jat.3153pt_PT
dc.identifier.issn0260-437X
dc.identifier.urihttp://hdl.handle.net/10400.18/3347
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Ltd.pt_PT
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/jat.3153/fullpt_PT
dc.subjectCa2+ Overloadpt_PT
dc.subjectApoptosispt_PT
dc.subjectCytotoxicitypt_PT
dc.subjectMitochondrial Hyperpolarizationpt_PT
dc.subjectPiperazine Designer Drugspt_PT
dc.subjectToxicologiapt_PT
dc.titleIn vitro neurotoxicity evaluation of piperazine designer drugs in differentiated human neuroblastoma SH-SY5Y cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/COMPETE/PEst-C%2FEQB%2FLA0006%2F2013/PT
oaire.citation.endPage130pt_PT
oaire.citation.startPage121pt_PT
oaire.citation.titleJournal of Applied Toxicologypt_PT
oaire.citation.volume36(1)pt_PT
oaire.fundingStreamCOMPETE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication0c766506-6307-4045-921c-39b8158f5e3c
relation.isProjectOfPublication.latestForDiscovery0c766506-6307-4045-921c-39b8158f5e3c

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