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Cocaine-induced kidney toxicity: an in vitro study using primary cultured human proximal tubular epithelial cells

dc.contributor.authorValente, Maria João
dc.contributor.authorHenrique, Rui
dc.contributor.authorVilas-Boas, Vânia
dc.contributor.authorSilva, Renata
dc.contributor.authorBastos, Maria de Lourdes
dc.contributor.authorCarvalho, Félix
dc.contributor.authorGuedes de Pinho, Paula
dc.contributor.authorCarvalho, Márcia
dc.date.accessioned2021-06-30T13:59:20Z
dc.date.available2021-06-30T13:59:20Z
dc.date.issued2011
dc.description.abstractRenal failure resulting from cocaine abuse has been well documented, although the underlying mechanisms remain to be investigated. In the present study, primary cultured human proximal tubular epithelial cells (HPTECs) of the kidney were used to investigate its ability to metabolize cocaine, as well as the cytotoxicity induced by cocaine and its metabolites benzoylecgonine (BE), ecgonine methyl ester (EME) and norcocaine (NCOC). Gas chromatography/ion trap-mass spectrometry (GC/IT-MS) analysis of HPTECs exposed to cocaine (1 mM) for 72 h confirmed its metabolism into EME and NCOC, but not BE. EME levels increased along the exposure time to cocaine, while NCOC concentration diminished after reaching a maximum at 6 h, indicating a possible secondary metabolism for this metabolite. Cocaine promoted a concentration-dependent loss of cell viability, whereas BE and EME were found to be non-toxic to HPTECs at the tested conditions. In contrast, NCOC revealed to have higher intrinsic nephrotoxicity than the parent compound. Moreover, cocaine-induced cell death was partially reversed in the presence of ketoconazole (KTZ), a potent CYP3A inhibitor, supporting the hypothesis that NCOC may play a role in cocaine-induced nephrotoxicity. Cocaine-induced cytotoxicity was found to involve intracellular glutathione depletion at low concentrations and to induce mitochondrial damage at higher concentrations. Under the present experimental conditions, HPTECs death pathway followed an apoptotic pattern, which was evident for concentrations as low as 0.1 mM.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1007/s00204-011-0749-3pt_PT
dc.identifier.eissn1432-0738
dc.identifier.issn0340-5761
dc.identifier.urihttp://hdl.handle.net/10284/9988
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.relationThis work has been supported by Fundação para a Ciência e a Tecnologia through grant no. PEst-C/EQB/LA0006/ 2011.pt_PT
dc.subjectCocainept_PT
dc.subjectNephrotoxicitypt_PT
dc.subjectHuman renal proximal tubular cellspt_PT
dc.subjectMetabolismpt_PT
dc.subjectApoptosispt_PT
dc.titleCocaine-induced kidney toxicity: an in vitro study using primary cultured human proximal tubular epithelial cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage261pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage249pt_PT
oaire.citation.titleArchives of Toxicologypt_PT
oaire.citation.volume86pt_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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