Repository logo
 
Publication

Neurotoxicity of β-Keto amphetamines: deathly mechanisms elicited by methylone and MDPV in human dopaminergic SH-SY5Y cells

2017Journal article Restricted access
Simple item page
dc.contributor.authorValente, Maria João
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorFernandes, Eduarda
dc.contributor.authorCarvalho, Félix
dc.contributor.authorGuedes de Pinho, Paula
dc.contributor.authorCarvalho, Márcia
dc.date.accessioned2021-07-02T14:53:39Z
dc.date.available2021-07-02T14:53:39Z
dc.date.issued2017
dc.description.abstractSynthetic cathinones (β-keto amphetamines) act as potent CNS stimulants similarly to classical amphetamines, which raise concerns about their potential neurotoxic effects. The present in vitro study aimed to explore and compare the mechanisms underlying the neurotoxicity of two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), with those of 3,4-methylenedioxymethamphetamine (MDMA), using undifferentiated and differentiated SH-SY5Y cells. Following a 24 h exposure period, methylone and MDPV induced loss of cell viability in a concentration-dependent manner, in the following order of potency: MDPV ≈ MDMA > methylone. Dopaminergic differentiated cells evidenced higher sensitivity to the neurotoxic effects of both cathinones and MDMA than the undifferentiated ones, but this effect was not inhibited by the DAT inhibitor GBR 12909. Intracellular oxidative stress mediated by methylone and MDPV was demonstrated by the increase in reactive oxygen and nitrogen species (ROS and RNS) production, depletion of intracellular reduced glutathione and increased oxidized glutathione levels. All three drugs elicited mitochondrial impairment, characterized by the mitochondrial membrane potential (Δψm) dissipation and intracellular ATP depletion. Apoptosis was found to be a common mechanism of cell death induced by methylone and MDPV, with evident chromatin condensation and formation of pyknotic nuclei, and activation of caspases 3, 8, and 9. In conclusion, the present data shows that oxidative stress and mitochondrial dysfunction play a role in cathinones-induced neuronal damage, ultimately leading to cell death by apoptosis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1021/acschemneuro.6b00421pt_PT
dc.identifier.issn1948-7193
dc.identifier.urihttp://hdl.handle.net/10284/10035
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherACS Publicationspt_PT
dc.relationPOCI/01/0145/FEDER/007728pt_PT
dc.relationApplied Molecular Biosciences Unit
dc.subjectβ-Keto amphetaminespt_PT
dc.subjectSynthetic cathinonespt_PT
dc.subjectNeurotoxicitypt_PT
dc.subjectOxidative stresspt_PT
dc.subjectMitochondrial impairmentpt_PT
dc.subjectApoptosispt_PT
dc.titleNeurotoxicity of β-Keto amphetamines: deathly mechanisms elicited by methylone and MDPV in human dopaminergic SH-SY5Y cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04378%2F2013/PT
oaire.citation.endPage859pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage850pt_PT
oaire.citation.titleACS Chemical Neurosciencept_PT
oaire.citation.volume8pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameCarvalho
person.givenNameMarcia
person.identifier2017111
person.identifier.ciencia-id8B10-171E-E63E
person.identifier.orcid0000-0001-9884-4751
person.identifier.ridD-5999-2013
person.identifier.scopus-author-id7201413997
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3837b828-ba57-47f7-a811-cce65e4922c6
relation.isAuthorOfPublication.latestForDiscovery3837b828-ba57-47f7-a811-cce65e4922c6
relation.isProjectOfPublication61924098-eb12-4752-9d4a-6e4243fc921d
relation.isProjectOfPublication.latestForDiscovery61924098-eb12-4752-9d4a-6e4243fc921d

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Neurotoxicity of β-Keto amphetamines.pdf
Size:
3.21 MB
Format:
Adobe Portable Document Format
Download

Collections

FCS - Artigos em Revistas Científicas Internacionais com Arbitragem Científica