PMID- 19333788
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20220408
IS  - 1559-0259 (Electronic)
IS  - 1530-7905 (Print)
IS  - 1530-7905 (Linking)
VI  - 9
IP  - 1
DP  - 2009 Mar
TI  - Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult 
      rat left ventricular myocytes.
PG  - 30-8
LID - 10.1007/s12012-009-9034-6 [doi]
AB  - 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.
FAU - Shenouda, Sylvia K
AU  - Shenouda SK
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, 
      USA.
FAU - Varner, Kurt J
AU  - Varner KJ
FAU - Carvalho, Felix
AU  - Carvalho F
FAU - Lucchesi, Pamela A
AU  - Lucchesi PA
LA  - eng
GR  - R01 HL063318/HL/NHLBI NIH HHS/United States
GR  - R01 HL63318-05/HL/NHLBI NIH HHS/United States
GR  - P20RR18766/RR/NCRR NIH HHS/United States
GR  - R01 HL063318-05/HL/NHLBI NIH HHS/United States
GR  - P20 RR018766-057610/RR/NCRR NIH HHS/United States
GR  - P20 RR018766/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090331
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (2,5-bis(glutathionyl)methyldopamine)
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - 555-64-6 (alpha-methyldopamine)
RN  - GAN16C9B8O (Glutathione)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Calcium Signaling/drug effects
MH  - Cells, Cultured
MH  - Deoxyepinephrine/analogs & derivatives/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Glutathione/analogs & derivatives/toxicity
MH  - Heart Ventricles/drug effects/metabolism/physiopathology
MH  - Male
MH  - Myocardial Contraction/*drug effects
MH  - Myocytes, Cardiac/*drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/metabolism/*toxicity
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Time Factors
PMC - PMC2859611
MID - NIHMS193762
EDAT- 2009/04/01 09:00
MHDA- 2009/06/12 09:00
PMCR- 2010/04/26
CRDT- 2009/04/01 09:00
PHST- 2009/02/11 00:00 [received]
PHST- 2009/03/18 00:00 [accepted]
PHST- 2009/04/01 09:00 [entrez]
PHST- 2009/04/01 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
PHST- 2010/04/26 00:00 [pmc-release]
AID - 10.1007/s12012-009-9034-6 [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2009 Mar;9(1):30-8. doi: 10.1007/s12012-009-9034-6. Epub 2009 
      Mar 31.