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The toxicity of N-methyl-α-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine

2004Journal article Restricted access
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dc.contributor.authorCarvalho, Márcia
dc.contributor.authorRemião, Fernando
dc.contributor.authorMilhazes, Nuno
dc.contributor.authorBorges, Fernanda
dc.contributor.authorFernandes, Eduarda
dc.contributor.authorCarvalho, Félix
dc.contributor.authorBastos, Maria de Lourdes
dc.date.accessioned2021-07-02T08:58:23Z
dc.date.available2021-07-02T08:58:23Z
dc.date.issued2004
dc.description.abstractIn the past decade, clinical evidence has increasingly shown that the liver is a target organ for 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") toxicity. The aims of the present in vitro study were: (1) to evaluate and compare the hepatotoxic effects of MDMA and one of its main metabolites, N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and (2) to investigate the ability of antioxidants, namely ascorbic acid and N-acetyl-L-cysteine (NAC), to prevent N-Me-alpha-MeDA-induced toxic injury, using freshly isolated rat hepatocytes. Cell suspensions were incubated with MDMA or N-Me-alpha-MeDA in the final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 3 h. To evaluate the potential protective effects of antioxidants, cells were preincubated with ascorbic acid in the final concentrations of 0.1 and 0.5 mM, or NAC in the final concentrations of 0.1 and 1 mM for 15 min before treatment with 1.6 mM N-Me-alpha-MeDA for 3 h (throughout this incubation period the cells were exposed to both compounds). The toxic effects were evaluated by measuring the cell viability, glutathione (GSH) and glutathione disulfide (GSSG), ATP, and the cellular activities of GSH peroxidase (GPX), GSSG reductase (GR), and GSH S-transferase (GST). MDMA induced a concentration- and time-dependent GSH depletion, but had a negligible effect on cell viability, ATP levels, or on the activities of GR, GPX, and GST. In contrast, N-Me-alpha-MeDA was shown to induce not only a concentration- and time-dependent depletion of GSH, but also a depletion of ATP levels accompanied by a loss in cell viability, and decreases in the antioxidant enzyme activities. For both compounds, GSH depletion was not accompanied by increases in GSSG levels, which seems to indicate GSH depletion by adduct formation. Importantly, the presence of ascorbic acid (0.5 mM) or NAC (1 mM) prevented cell death and GSH depletion induced by N-Me-alpha-MeDA. The results provide evidence that MDMA and its metabolite N-Me-alpha-MeDA induce toxicity to freshly isolated rat hepatocytes. Oxidative stress may play a major role in N-Me-alpha-MeDA-induced hepatic toxicity since antioxidant defense systems are impaired and administration of antioxidants prevented N-Me-alpha-MeDA toxicity.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.tox.2004.03.016pt_PT
dc.identifier.issn0300-483X
dc.identifier.urihttp://hdl.handle.net/10284/10010
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationThis work was supported by Ph.D. grants from FCT (Praxis XXI/BD/20087/99 and Praxis XXI/BD/18520/ 98) and POCTI, Portugal, and by FEDER European Community funding (Project POCTI/36099/FCB/2000).pt_PT
dc.subjectEcstasypt_PT
dc.subjectN-methyl-a-methyldopaminept_PT
dc.subjectToxicitypt_PT
dc.subjectHepatocytespt_PT
dc.subjectOxidative stresspt_PT
dc.subjectAntioxidantspt_PT
dc.subjectAscorbic acidpt_PT
dc.subjectN-acetylcysteinept_PT
dc.titleThe toxicity of N-methyl-α-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteinept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage203pt_PT
oaire.citation.issue2-3pt_PT
oaire.citation.startPage193pt_PT
oaire.citation.titleToxicologypt_PT
oaire.citation.volume200pt_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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