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3,4-Methylenedioxymethamphetamine alters left ventricular function and activates nuclear factor-Kappa B (NF-κB) in a time and dose dependent manner.

Tiangco DA, Halcomb S, Lattanzio FA, Hargrave BY - Int J Mol Sci (2010)

Bottom Line: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described.We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.

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-κB) 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 μM MDMA for 12 h caused increased nuclear localization of NF-κB 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-κB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset.

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ELISA for NF-κB nuclear localization (mean ± SD). Either 0 mM MDMA (media only) (n = 3) or 1 mM MDMA (n = 3) was used at each time point. Each experiment was performed independently. A kit-provided assay-level positive control (+Control) of nuclear extracts prepared from IL-1β treated HeLa cells was included during the plate run. * p < 0.05.
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f12-ijms-11-04843: ELISA for NF-κB nuclear localization (mean ± SD). Either 0 mM MDMA (media only) (n = 3) or 1 mM MDMA (n = 3) was used at each time point. Each experiment was performed independently. A kit-provided assay-level positive control (+Control) of nuclear extracts prepared from IL-1β treated HeLa cells was included during the plate run. * p < 0.05.

Mentions: We observed a significant increase in nuclear localization of NF-κB in H9c2 cells exposed to 1.0 mM MDMA at the 6 h time point (Figure 12). Measurements taken at the 3 h and 12 h time points for cells exposed to 1 mM MDMA were not significantly different from their paired controls. We also observed significant nuclear localization of NF-κB with the 2.0 μM dose, however this occurred at the 12 h time point (Figure 13). In addition, we did not observe a significant difference in NF-κB activity between the placebo and MDMA groups in myocardial tissue specimens from our functional experiments (data not shown).


3,4-Methylenedioxymethamphetamine alters left ventricular function and activates nuclear factor-Kappa B (NF-κB) in a time and dose dependent manner.

Tiangco DA, Halcomb S, Lattanzio FA, Hargrave BY - Int J Mol Sci (2010)

ELISA for NF-κB nuclear localization (mean ± SD). Either 0 mM MDMA (media only) (n = 3) or 1 mM MDMA (n = 3) was used at each time point. Each experiment was performed independently. A kit-provided assay-level positive control (+Control) of nuclear extracts prepared from IL-1β treated HeLa cells was included during the plate run. * p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100831&req=5

f12-ijms-11-04843: ELISA for NF-κB nuclear localization (mean ± SD). Either 0 mM MDMA (media only) (n = 3) or 1 mM MDMA (n = 3) was used at each time point. Each experiment was performed independently. A kit-provided assay-level positive control (+Control) of nuclear extracts prepared from IL-1β treated HeLa cells was included during the plate run. * p < 0.05.
Mentions: We observed a significant increase in nuclear localization of NF-κB in H9c2 cells exposed to 1.0 mM MDMA at the 6 h time point (Figure 12). Measurements taken at the 3 h and 12 h time points for cells exposed to 1 mM MDMA were not significantly different from their paired controls. We also observed significant nuclear localization of NF-κB with the 2.0 μM dose, however this occurred at the 12 h time point (Figure 13). In addition, we did not observe a significant difference in NF-κB activity between the placebo and MDMA groups in myocardial tissue specimens from our functional experiments (data not shown).

Bottom Line: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described.We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.

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-κB) 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 μM MDMA for 12 h caused increased nuclear localization of NF-κB 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-κB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset.

Show MeSH
Related in: MedlinePlus