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Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A

2009-04Journal article Open access
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dc.contributor.authorAlves, Ema
dc.contributor.authorSummavielle, Teresa
dc.contributor.authorAlves, Cecília Juliana
dc.contributor.authorCustódio, José Barata Antunes
dc.contributor.authorFernandes, Eduarda
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorTavares, Maria Amélia
dc.contributor.authorCarvalho, Félix
dc.date.accessioned2021-09-28T07:38:15Z
dc.date.available2021-09-28T07:38:15Z
dc.date.issued2009-04
dc.description.abstractThe administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlves, E., Summavielle, T., Alves, C. J., Custódio, J. B. A., Fernandes, E., De Lourdes Bastos, M., Tavares, M. A., & Carvalho, F. (2009). Preclinical Study: Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A. Addiction Biology, 14(2), 185-193. 10.1111/j.1369-1600.2008.00143.xpt_PT
dc.identifier.doi10.1111/j.1369-1600.2008.00143.xpt_PT
dc.identifier.issn1369-1600
dc.identifier.urihttp://hdl.handle.net/10400.22/18578
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWilleypt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1111/j.1369-1600.2008.00143.xpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subject3pt_PT
dc.subject4-methylenedioxymethamphetaminept_PT
dc.subjectBrain mitochondriapt_PT
dc.subjectHyperthermiapt_PT
dc.subjectMonoamine oxidase Apt_PT
dc.subjectNeurotoxicitypt_PT
dc.subjectOxidative stresspt_PT
dc.titleEcstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type Apt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage193pt_PT
oaire.citation.startPage185pt_PT
oaire.citation.titleAddiction Biologypt_PT
oaire.citation.volume14pt_PT
person.familyNameSummavielle
person.givenNameTeresa
person.identifier677706
person.identifier.ciencia-idC41E-0816-5C85
person.identifier.orcid0000-0003-2548-6281
person.identifier.ridC-9776-2012
person.identifier.scopus-author-id6603092949
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication207ee2de-85a0-4144-9e7e-b376c600e065
relation.isAuthorOfPublication.latestForDiscovery207ee2de-85a0-4144-9e7e-b376c600e065

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