Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.
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.
Song
Byoung-Joon
BJ
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD 20892, USA. bj.song@nih.gov
Moon
Kwan-Hoon
KH
Upreti
Vijay V
VV
Eddington
Natalie D
ND
Lee
Insong J
IJ
D000818:Animals; D006213:Hallucinogens / Q000633:toxicity; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D008954:Models, Biological; D009102:Multiple Organ Failure / Q000139:chemically induced* / Q000503:physiopathology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D014781:Viscera / Q000187:drug effects*
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine