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

Abstract

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

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Citations

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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