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dc.contributor.authorTirri, Micaela
dc.contributor.authorFrisoni, Paolo
dc.contributor.authorBilel, Sabrine
dc.contributor.authorArfè, Raffaella
dc.contributor.authorTrapella, Claudio
dc.contributor.authorFantinati, Anna
dc.contributor.authorCorli, Giorgia
dc.contributor.authorMarchetti, Beatrice
dc.contributor.authorDe-Giorgio, Fabio
dc.contributor.authorCamuto, Cristian
dc.contributor.authorMazzarino, Monica
dc.contributor.authorGaudio, Rosa Maria
dc.contributor.authorSerpelloni, Giovanni
dc.contributor.authorSchifano, Fabrizio
dc.contributor.authorBotrè, Francesco
dc.contributor.authorMarti, Matteo
dc.date.accessioned2021-08-19T11:30:03Z
dc.date.available2021-08-19T11:30:03Z
dc.date.issued2021-08-16
dc.identifier.citationTirri , M , Frisoni , P , Bilel , S , Arfè , R , Trapella , C , Fantinati , A , Corli , G , Marchetti , B , De-Giorgio , F , Camuto , C , Mazzarino , M , Gaudio , R M , Serpelloni , G , Schifano , F , Botrè , F & Marti , M 2021 , ' Worsening of the Toxic Effects of (±) Cis -4,4′-DMAR Following Its Co-Administration with (±) Trans -4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice ' , International Journal of Molecular Sciences , vol. 22 , no. 16 , 8771 . https://doi.org/10.3390/ijms22168771
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 25791377
dc.identifier.otherPURE UUID: 00ed94c0-0fad-418c-823f-e0c239c2034c
dc.identifier.otherJisc: a58a45952bdc4fe9bdcfea1cd4ce921b
dc.identifier.otherPubMed: 34445476
dc.identifier.otherScopus: 85112532651
dc.identifier.urihttp://hdl.handle.net/2299/24986
dc.description© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).
dc.description.abstract4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4′-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers’ co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.en
dc.format.extent25
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.rightsOpen
dc.subject4-4′-DMAR
dc.subjectimmunohistochemistry
dc.subjectdrug metabolism
dc.subjecthyperthermia
dc.subjectnovel psychoactive substances
dc.subjectstimulant
dc.subjectoxidative/nitrosative stress
dc.subjectapoptosis
dc.subjectneurotoxicity
dc.subjectcortex
dc.subjectImmunohistochemistry
dc.subjectNovel psychoactive substances
dc.subjectStimulant
dc.subjectCortex
dc.subjectNeurotoxicity
dc.subject4-4 -DMAR
dc.subjectOxidative/nitrosative stress
dc.subjectDrug metabolism
dc.subjectHyperthermia
dc.subjectApoptosis
dc.subjectStereoisomerism
dc.subjectMale
dc.subjectPsychotropic Drugs/classification
dc.subjectBehavior, Animal/drug effects
dc.subjectMice, Inbred ICR
dc.subjectAnimals
dc.subjectOxazoles/classification
dc.subjectMice
dc.subjectPsychophysiologic Disorders/chemically induced
dc.subjectMolecular Biology
dc.subjectSpectroscopy
dc.subjectCatalysis
dc.subjectInorganic Chemistry
dc.subjectComputer Science Applications
dc.subjectPhysical and Theoretical Chemistry
dc.subjectOrganic Chemistry
dc.titleWorsening of the Toxic Effects of (±) Cis -4,4′-DMAR Following Its Co-Administration with (±) Trans -4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Miceen
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionPsychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85112532651&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2021-08-16
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.3390/ijms22168771
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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