Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells

Toxicology Letters
Patrícia Silva FerreiraJoão Paulo Capela

Abstract

"Ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans. MDMA metabolites can be major contributors for MDMA neurotoxicity. This work studied the neurotoxicity of MDMA and its catechol metabolites, α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) in human dopaminergic SH-SY5Y cells differentiated with retinoic acid and 12-O-tetradecanoyl-phorbol-13-acetate. Differentiation led to SH-SY5Y neurons with higher ability to accumulate dopamine and higher resistance towards dopamine neurotoxicity. MDMA catechol metabolites were neurotoxic to SH-SY5Y neurons, leading to caspase 3-independent cell death in a concentration- and time-dependent manner. MDMA did not show a concentration- and time-dependent death. Pre-treatment with the antioxidant and glutathione precursor, N-acetylcysteine (NAC), resulted in strong protection against the MDMA metabolites' neurotoxicity. Neither the superoxide radical scavenger, tiron, nor the inhibitor of the dopamine (DA) transporter, GBR 12909, prevented the metabolites' toxicity. Cells exposed to α-MeDA showed an increase in intracellular glutathione (GSH) levels, whi...Continue Reading

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Citations

Nov 2, 2013·Archives of Toxicology·Daniel José BarbosaFélix Carvalho
May 28, 2013·Journal of Toxicology·João Barbosa MartinsJoão Paulo Capela
Oct 13, 2015·Progress in Neurobiology·Rosario MoratallaMicaela Morelli
Nov 12, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C DowneyK M O'Boyle
Jun 29, 2016·BMC Pharmacology & Toxicology·Armanda Teixeira-GomesJoão Paulo Capela
Sep 26, 2015·Pharmacological Reviews·Esa R KorpiGavin S Dawe
Jun 24, 2018·Neurotoxicity Research·Teresa CocciniUliana De Simone
Mar 21, 2020·Archives of Toxicology·Daniela Ferreira RodriguesFélix Carvalho
Jul 8, 2017·Neuroscience Letters·Susan M LantzSyed F Ali

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