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Editor’s highlight: characterization of hepatotoxicity mechanisms triggered by designer cathinone drugs (β-Keto amphetamines)

2016Journal article Restricted access
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dc.contributor.authorValente, Maria João
dc.contributor.authorAraújo, Ana Margarida
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorFernandes, Eduarda
dc.contributor.authorCarvalho, Félix
dc.contributor.authorGuedes de Pinho, Paula
dc.contributor.authorCarvalho, Márcia
dc.date.accessioned2021-07-02T11:54:49Z
dc.date.available2021-07-02T11:54:49Z
dc.date.issued2016
dc.description.abstractThe use of cathinone designer drugs in recreational settings has been associated with severe toxic effects, including liver damage. The precise mechanisms by which cathinones induce hepatotoxicity and whether they act by common pathways remain to be elucidated. Herein, we assessed the toxicity of the cathinones methylone, pentedrone, 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylethcathinone (4-MEC) in primary rat hepatocytes (PRH) and HepaRG cells, and compared with that of 3,4-methylenedioxymethamphetamine (MDMA). MDPV and pentedrone were significantly more toxic than MDMA, while methylone was the least cytotoxic compound. Importantly, PRH revealed to be the most sensitive experimental model and was thus used to explore the mechanisms underlying the observed toxicity. All drugs elicited the formation of reactive oxygen and nitrogen species (ROS and RNS), but more markedly for methylone, pentedrone and 4-MEC. GSH depletion was also a common effect at the highest concentration tested, whereas only MDPV and pentedrone caused a significant decrease in ATP levels. The antioxidants ascorbic acid or N-acetyl-L-cysteine partially attenuated the observed cell death. All cathinones triggered significant caspase activation and apoptosis, which was partially reversed by the caspase inhibitor Ac-LETD-CHO. In conclusion, the present data shows that (1) cathinones induce in vitro hepatotoxic effects that vary in magnitude among the different analogues, (2) oxidative stress and mitochondrial dysfunction play a role in cathinones-induced hepatic injury, and (3) apoptosis appears to be an important pathway of cell death elicited by these novel drugs.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1093/toxsci/kfw105pt_PT
dc.identifier.eissn1096-0929
dc.identifier.issn1096-6080
dc.identifier.urihttp://hdl.handle.net/10284/10023
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relationThis work was supported by National Funds from Fundação para a Ciência e Tecnologia and Fundo Europeu de Desenvolvimento Regional under Program PT2020 (007265-UID/ QUI/50006/2013) and partially from Fundação para a Ciência e Tecnologia funds (UID/Multi/04546/2013). M.J.V. thanks Fundação para a Ciência e Tecnologia for her PhD Grant (SFRH/ BD/89879/2012)pt_PT
dc.subjectSynthetic cathinonespt_PT
dc.subjectβ-keto amphetaminespt_PT
dc.subjectHepatotoxicitypt_PT
dc.subjectOxidative stresspt_PT
dc.subjectApoptosispt_PT
dc.titleEditor’s highlight: characterization of hepatotoxicity mechanisms triggered by designer cathinone drugs (β-Keto amphetamines)pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage102pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage89pt_PT
oaire.citation.titleToxicological Sciencespt_PT
oaire.citation.volume153pt_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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