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The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells

2020Journal article Restricted access
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dc.contributor.authorVaz, I.
dc.contributor.authorCarvalho, T.
dc.contributor.authorValente, M.J.
dc.contributor.authorCastro, A.
dc.contributor.authorAraújo, A.M.
dc.contributor.authorBastos, M.L.
dc.contributor.authorCarvalho, Márcia
dc.date.accessioned2021-07-02T09:32:00Z
dc.date.available2021-07-02T09:32:00Z
dc.date.issued2020
dc.description.abstractSynthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC > MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.toxlet.2020.05.025pt_PT
dc.identifier.issn0378-4274
dc.identifier.urihttp://hdl.handle.net/10284/10013
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationThis work was supported by the Applied Molecular Biosciences Unit (UCIBIO), Portugal, which is financed by National Funds from Fundação para a Ciência e a Tecnologia (FCT), Portugal (UIDB/04378/ 2020). A.M. Araújo thanks FCT, Portugal, for her PhD fellowship grant (SFRH/BD/107708/2015) and M. Carvalho also acknowledges FCT through the UID/MULTI/04546/2019 project.pt_PT
dc.subjectSynthetic cathinonespt_PT
dc.subjectNephrotoxicitypt_PT
dc.subjectOxidative stresspt_PT
dc.subjectApoptosispt_PT
dc.subjectAutophagypt_PT
dc.subjectAntioxidantspt_PT
dc.titleThe interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage52pt_PT
oaire.citation.startPage42pt_PT
oaire.citation.titleToxicology Letterspt_PT
oaire.citation.volume331pt_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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