The mixture of "ecstasy" and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations

Archives of Toxicology
Daniel José BarbosaFélix Carvalho


The neurotoxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) is thought to involve hepatic metabolism, though its real contribution is not completely understood. Most in vitro neurotoxicity studies concern isolated exposures of MDMA or its metabolites, at high concentrations, not considering their mixture, as expected in vivo. Therefore, our postulate is that combined deleterious effects of MDMA and its metabolites, at low micromolar concentrations that may be attained into the brain, may elicit neurotoxicity. Using human SH-SY5Y differentiated cells as dopaminergic neuronal model, we studied the neurotoxicity of MDMA and its MDMA metabolites α-methyldopamine and N-methyl-α-methyldopamine and their correspondent glutathione and N-acetylcysteine monoconjugates, under isolated exposure and as a mixture, at normothermic or hyperthermic conditions. The results showed that the mixture of MDMA and its metabolites was toxic to SH-SY5Y differentiated cells, an effect potentiated by hyperthermia and prevented by N-acetylcysteine. As a mixture, MDMA and its metabolites presented a different toxicity profile, compared to each compound alone, even at equimolar concentrations. Caspase 3 activation, increased reactive oxygen spec...Continue Reading


May 13, 1986·European Journal of Pharmacology·C J SchmidtW Lovenberg
Feb 15, 2000·British Journal of Clinical Pharmacology·Rafael de la TorreJ Camí
Dec 26, 2001·Brain Research·Henry N NguyenDavid C Perry
May 18, 2004·Chemical Research in Toxicology·Márcia CarvalhoMaria Lourdes Bastos
Sep 24, 2004·Trends in Pharmacological Sciences·Rafael de la Torre, Magi Farre
Jan 7, 2005·The Journal of Pharmacology and Experimental Therapeutics·Douglas C JonesTerrence J Monks
Apr 14, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mark A TirmensteinLester W Schwartz
Sep 27, 2005·The Journal of Pharmacology and Experimental Therapeutics·João Paulo CapelaFélix Carvalho
Dec 2, 2006·Trends in Neurosciences·Takumi Satoh, Stuart A Lipton
May 1, 2007·Neuroscience·João Paulo CapelaFélix Carvalho
Jun 19, 2007·Neurotoxicology·João Paulo CapelaFélix Carvalho
Oct 2, 2007·The Journal of Pharmacology and Experimental Therapeutics·Gladys V ErivesTerrence J Monks
Dec 15, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shaik Shavali, Donald A Sens
Sep 23, 2008·Journal of Neuroscience Research·Hiroki TakeuchiShun Shimohama
Oct 1, 2008·Journal of Neurochemistry·Noelia GranadoRosario Moratalla
Dec 25, 2008·The Journal of Biological Chemistry·Jorge Ma Oliveira, Jorge Gonçalves
Apr 18, 2009·Molecular Neurobiology·João Paulo CapelaFélix Carvalho
Jul 25, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Melanie MuellerGeorge A Ricaurte
Feb 23, 2010·PloS One·Clara TouriñoOlga Valverde
Jul 17, 2010·The Journal of Pharmacology and Experimental Therapeutics·Bethann N Johnson, Bryan K Yamamoto
Oct 22, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Seth W PerryHarris A Gelbard
Apr 22, 2011·British Journal of Pharmacology·Daniel José BarbosaFélix Carvalho
Oct 7, 2011·Trends in Pharmacological Sciences·Charmaine S Ferguson, Rachel F Tyndale


Nov 2, 2013·Archives of Toxicology·Daniel José BarbosaFélix Carvalho
Apr 25, 2014·Chemico-biological Interactions·Renata SilvaFernando Remião
Feb 14, 2014·Archives of Toxicology·Daniel José BarbosaEduardo Soriano
Mar 7, 2015·Archives of Toxicology·Daniel José BarbosaFélix Carvalho
Jul 28, 2016·Free Radical Biology & Medicine·Ghorban TaghizadehMohammad Sharifzadeh
Mar 7, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Daniel José BarbosaFélix Carvalho
Apr 23, 2015·Journal of Applied Toxicology : JAT·Marcelo Dutra ArboHelena Carmo
Nov 23, 2019·Journal of Applied Toxicology : JAT·Caroline SoutoMarcelo Dutra Arbo
Jun 6, 2018·Archives of Toxicology·R Feio-AzevedoJoão Paulo Capela
Jun 24, 2018·Neurotoxicity Research·Teresa CocciniUliana De Simone
Feb 23, 2020·International Journal of Molecular Sciences·Huey Sze LeongShanlin Fu
Jan 2, 2021·International Journal of Molecular Sciences·Sara SilvaNuno Vale
Jul 8, 2017·Neuroscience Letters·Susan M LantzSyed F Ali

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