dc.contributor.author | Tirri, Micaela | |
dc.contributor.author | Frisoni, Paolo | |
dc.contributor.author | Bilel, Sabrine | |
dc.contributor.author | Arfè, Raffaella | |
dc.contributor.author | Trapella, Claudio | |
dc.contributor.author | Fantinati, Anna | |
dc.contributor.author | Corli, Giorgia | |
dc.contributor.author | Marchetti, Beatrice | |
dc.contributor.author | De-Giorgio, Fabio | |
dc.contributor.author | Camuto, Cristian | |
dc.contributor.author | Mazzarino, Monica | |
dc.contributor.author | Gaudio, Rosa Maria | |
dc.contributor.author | Serpelloni, Giovanni | |
dc.contributor.author | Schifano, Fabrizio | |
dc.contributor.author | Botrè, Francesco | |
dc.contributor.author | Marti, Matteo | |
dc.date.accessioned | 2021-08-19T11:30:03Z | |
dc.date.available | 2021-08-19T11:30:03Z | |
dc.date.issued | 2021-08-16 | |
dc.identifier.citation | Tirri , 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 (IJMS) , vol. 22 , no. 16 , 8771 . https://doi.org/10.3390/ijms22168771 | |
dc.identifier.issn | 1661-6596 | |
dc.identifier.other | Jisc: a58a45952bdc4fe9bdcfea1cd4ce921b | |
dc.identifier.uri | http://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.abstract | 4,4’-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.extent | 25 | |
dc.format.extent | 3050818 | |
dc.language.iso | eng | |
dc.relation.ispartof | International Journal of Molecular Sciences (IJMS) | |
dc.subject | 4-4′-DMAR | |
dc.subject | immunohistochemistry | |
dc.subject | drug metabolism | |
dc.subject | hyperthermia | |
dc.subject | novel psychoactive substances | |
dc.subject | stimulant | |
dc.subject | oxidative/nitrosative stress | |
dc.subject | apoptosis | |
dc.subject | neurotoxicity | |
dc.subject | cortex | |
dc.subject | Immunohistochemistry | |
dc.subject | Novel psychoactive substances | |
dc.subject | Stimulant | |
dc.subject | Cortex | |
dc.subject | Neurotoxicity | |
dc.subject | 4-4 -DMAR | |
dc.subject | Oxidative/nitrosative stress | |
dc.subject | Drug metabolism | |
dc.subject | Hyperthermia | |
dc.subject | Apoptosis | |
dc.subject | Stereoisomerism | |
dc.subject | Male | |
dc.subject | Psychotropic Drugs/classification | |
dc.subject | Behavior, Animal/drug effects | |
dc.subject | Mice, Inbred ICR | |
dc.subject | Animals | |
dc.subject | Oxazoles/classification | |
dc.subject | Mice | |
dc.subject | Psychophysiologic Disorders/chemically induced | |
dc.subject | Molecular Biology | |
dc.subject | Spectroscopy | |
dc.subject | Catalysis | |
dc.subject | Inorganic Chemistry | |
dc.subject | Computer Science Applications | |
dc.subject | Physical and Theoretical Chemistry | |
dc.subject | Organic Chemistry | |
dc.title | 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 | en |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.contributor.institution | Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.description.status | Peer reviewed | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85112532651&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.3390/ijms22168771 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |