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01-03-2009

Metabolites of MDMA Induce Oxidative Stress and Contractile Dysfunction in Adult Rat Left Ventricular Myocytes

Authors: Sylvia K. Shenouda, Kurt J. Varner, Felix Carvalho, Pamela A. Lucchesi

Published in: Cardiovascular Toxicology | Issue 1/2009

Abstract

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown, oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-cysteine (NAC). The metabolites of MDMA, but not MDMA alone, significantly decreased contractility and impaired relaxation in myocytes stimulated at 1 Hz. These effects were prevented by NAC. Together, these data suggest that MDMA-induced oxidative stress in the left ventricle can be due, at least in part, to the metabolism of MDMA to redox active metabolites.

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Title: Metabolites of MDMA Induce Oxidative Stress and Contractile Dysfunction in Adult Rat Left Ventricular Myocytes
Authors: Sylvia K. Shenouda
Kurt J. Varner
Felix Carvalho
Pamela A. Lucchesi
Publication date: 01-03-2009
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 1/2009
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-009-9034-6

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Metabolites of MDMA Induce Oxidative Stress and Contractile Dysfunction in Adult Rat Left Ventricular Myocytes

Abstract

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