Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

Author(s): Byoung-Joon Song, Kwan-Hoon Moon, Vijay V. Upreti, Natalie D. Eddington, Insong J. Lee.

Journal Name: Current Pharmaceutical Biotechnology

Volume 11 , Issue 5 , 2010

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Abstract:

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4- methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage.

Keywords: MDMA, metabolism, oxidative/nitrosative stress, protein oxidation, functional redox proteomics, mitochondrial dysfunction, organ damage

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Article Details

VOLUME: 11
ISSUE: 5
Year: 2010
Page: [434 - 443]
Pages: 10
DOI: 10.2174/138920110791591436
Price: $58

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