Repository logo
 
Publication

3,4-Methylenedioxymethamphetamine hepatotoxicity under the heat stress condition: novel insights from in vitro metabolomic studies

2020Journal article Restricted access
Simple item page
dc.contributor.authorAraújo, Ana Margarida
dc.contributor.authorEnea, Maria
dc.contributor.authorFernandes, Eduarda
dc.contributor.authorCarvalho, Félix
dc.contributor.authorde Lourdes Bastos, Maria
dc.contributor.authorCarvalho, Márcia
dc.contributor.authorGuedes de Pinho, Paula
dc.date.accessioned2021-06-30T09:31:45Z
dc.date.available2021-06-30T09:31:45Z
dc.date.issued2020
dc.description.abstractHyperthermia has been extensively reported as a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. In this work, we used a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry to evaluate the impact of hyperthermia on the hepatic metabolic changes caused by MDMA. For this purpose, primary mouse hepatocytes were exposed to subtoxic (LC01 and LC10) and toxic (LC30) concentrations of MDMA for 24 h, at 37 or 40.5 °C (simulating body temperature increase after MDMA consumption), and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed that metabolic patterns clearly discriminate MDMA treated cells from control cells, both in normothermic and hyperthermic conditions. The metabolic signature was found to be largely common to MDMA subtoxic and toxic concentrations, although with evident differences in the magnitude of response, with metabolic changes significantly more pronounced at 40.5 °C. Discriminant metabolites associated with MDMA-induced hepatotoxicity are mostly involved in the amino acid metabolism, aminoacyl tRNA biosynthesis, glutathione metabolism, tricarboxylic acid cycle, and pyruvate metabolism. Moreover, our metabolomic findings were corroborated by classical toxicity parameters, demonstrating the high sensitivity of this omic approach to assess molecular-level effects. Overall, this study indicates that MDMA triggers significant metabolic alterations on hepatic cells, even at low concentrations, that are clearly exacerbated at high temperatures. These findings provide new metabolic pieces to solve the puzzle of MDMA's hepatotoxicity mechanism and emphasize the increased risks of MDMA abuse due to the thermogenic action of the drug.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1021/acs.jproteome.9b00741pt_PT
dc.identifier.eissn1535-3907
dc.identifier.issn1535-3893
dc.identifier.urihttp://hdl.handle.net/10284/9976
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherACS Publicationspt_PT
dc.relationThis work was supported by the Applied Molecular Biosciences Unit − UCIBIO which is financed by national funds from FCT (UIDB/04378/2020). A.M.A. and M.E. thank FCT for their PhD fellowships (SFRH/BD/107708/2015 and PD/BD/109634/2015, respectively), and M.C. also acknowl- edges FCT through the UID/MULTI/04546/2019 project.pt_PT
dc.subjectHyperthermiapt_PT
dc.subjectMDMApt_PT
dc.subjectIn vitropt_PT
dc.subjectHepatotoxicitypt_PT
dc.subjectMetabolomicspt_PT
dc.subjectGC−MSpt_PT
dc.title3,4-Methylenedioxymethamphetamine hepatotoxicity under the heat stress condition: novel insights from in vitro metabolomic studiespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1234pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage1222pt_PT
oaire.citation.titleJournal of Proteome Researchpt_PT
oaire.citation.volume19pt_PT
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
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication3837b828-ba57-47f7-a811-cce65e4922c6
relation.isAuthorOfPublication.latestForDiscovery3837b828-ba57-47f7-a811-cce65e4922c6

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
3,4-Methylenedioxymethamphetamine hepatotoxicity under the heat stress condition: novel insights from in vitro metabolomic studies.pdf
Size:
3.48 MB
Format:
Adobe Portable Document Format
Download

Collections

FCS - Artigos em Revistas Científicas Internacionais com Arbitragem Científica