Next Article in Journal
Screening and Initial Binding Assessment of Fumonisin B1 Aptamers
Next Article in Special Issue
Dextran Sulfate Sodium Inhibits Alanine Synthesis in Caco-2 Cells
Previous Article in Journal
An Adsorptive Transfer Technique Coupled with Brdicka Reaction to Reveal the Importance of Metallothionein in Chemotherapy with Platinum Based Cytostatics
Previous Article in Special Issue
Functional Toxicogenomics: Mechanism-Centered Toxicology
Int. J. Mol. Sci. 2010, 11(12), 4843-4863; doi:10.3390/ijms11124743
Article

3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-kB) in a Time and Dose Dependent Manner

1, 1, Jr. 2 and 1,*
Received: 13 October 2010; in revised form: 4 November 2010 / Accepted: 8 November 2010 / Published: 26 November 2010
(This article belongs to the Special Issue Advances in Molecular Toxicology)
View Full-Text   |   Download PDF [336 KB, uploaded 19 June 2014]   |   Browse Figures
Abstract: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described. In the current study, we observed the effects of acute MDMA on rabbit left ventricular function. We also observed the effects of MDMA on nuclear factor-kappa B (NF-kB) activity in cultured rat ventricular myocytes (H9c2). In the rabbit, MDMA (2 mg/kg) alone caused a significant increase in heart rate and a significant decrease in the duration of the cardiac cycle. Inhibition of nitric oxide synthase (NOS) by pretreatment with L-NAME (10 mg/kg) alone caused significant dysfunction in heart rate, systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean left ventricular pressure. Pretreatment with L-NAME followed by treatment with MDMA caused significant dysfunction in additional parameters that were not abnormal upon exposure to either compound in isolation: duration of contraction, inotropy, and pulse pressure. Exposure to 1.0 mM MDMA for 6 h or 2.0 mM MDMA for 12 h caused increased nuclear localization of NF-kB in cultured H9c2 cells. The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters. The delayed timing of NF-kB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset.
Keywords: MDMA; ecstasy; NF-kB; nuclear; iNOS; H9c2; cardiac myocytes; rabbit MDMA; ecstasy; NF-kB; nuclear; iNOS; H9c2; cardiac myocytes; rabbit
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Tiangco, D.A.; Halcomb, S.; Lattanzio, F.A., Jr.; Hargrave, B.Y. 3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-kB) in a Time and Dose Dependent Manner. Int. J. Mol. Sci. 2010, 11, 4843-4863.

AMA Style

Tiangco DA, Halcomb S, Lattanzio FA, Jr, Hargrave BY. 3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-kB) in a Time and Dose Dependent Manner. International Journal of Molecular Sciences. 2010; 11(12):4843-4863.

Chicago/Turabian Style

Tiangco, David A.; Halcomb, Sapna; Lattanzio, Frank A., Jr.; Hargrave, Barbara Y. 2010. "3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-kB) in a Time and Dose Dependent Manner." Int. J. Mol. Sci. 11, no. 12: 4843-4863.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert