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Effect of temperature on 3,4-Methylenedioxypyrovalerone (MDPV)-induced metabolome disruption in primary mouse hepatic cells

2020Journal article Restricted access
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dc.contributor.authorAraújo, Ana Margarida
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorCarvalho, Félix
dc.contributor.authorGuedes de Pinho, Paula
dc.contributor.authorCarvalho, Márcia
dc.date.accessioned2021-07-02T09:26:00Z
dc.date.available2021-07-02T09:26:00Z
dc.date.issued2020
dc.description.abstract3,4-Methylenedioxypyrovalerone (MDPV) is one of the most popular cathinone derivatives worldwide and has recently been associated with several intoxications and deaths, in which, similarly to amphetamines, hyperthermia appears to play a prominent role. However, there remains a huge information gap underlying the mechanisms associated with its hepatotoxicity, namely under hyperthermic conditions. Here, we use a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry (GC-MS) to investigate the effect of subtoxic and toxic concentrations of MDPV on the metabolic profile of primary mouse hepatocytes (PMH), under normothermic and hyperthermic conditions. For this purpose, hepatocytes were exposed to increasing concentrations of MDPV (LC01, LC10 and LC30) for 24 h, at 37 °C or 40.5 °C, and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed a clear separation between MDPV exposed cells and control cells in normothermic conditions, even at subtoxic concentrations (LC01 and LC10). In normothermia, there was a significant dysregulation of pathways associated with ascorbate metabolism, tricarboxylic acid (TCA) cycle and pyruvate metabolism. These metabolic changes were significantly increased at 40.5 °C, and several other pathways appear to be affected with the evolution of toxicity caused by MDPV under hyperthermic conditions, namely aspartate and glutamate metabolism, phenylalanine and tyrosine biosynthesis, aminoacyl-tRNA biosynthesis, butanoate metabolism, among others. Overall, our findings provide novel insights into the mechanism of hepatotoxicity triggered by MDPV and highlight the higher risks that may occur under hyperthermic conditions.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.tox.2020.152503pt_PT
dc.identifier.issn0300-483X
dc.identifier.urihttp://hdl.handle.net/10284/10012
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_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. Araújo thanks to FCT for her Ph.D. fellowships (SFRH/BD/ 107708/2015) and M. Carvalho also acknowledges FCT through the UID/MULTI/04546/2019 project.pt_PT
dc.subjectMDPVpt_PT
dc.subjectHyperthermiapt_PT
dc.subjectPrimary mouse hepatocytespt_PT
dc.subjectHepatotoxicitypt_PT
dc.subjectMetabolomicspt_PT
dc.subjectGC–MSpt_PT
dc.titleEffect of temperature on 3,4-Methylenedioxypyrovalerone (MDPV)-induced metabolome disruption in primary mouse hepatic cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage13pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleToxicologypt_PT
oaire.citation.volume441pt_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

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