Cocaine, not morphine, causes the generation of reactive oxygen species and activation of NF-κB in transiently cotransfected heart cells

  title={Cocaine, not morphine, causes the generation of reactive oxygen species and activation of NF-$\kappa$B in transiently cotransfected heart cells},
  author={Barbara Y. Hargrave and David A. Tiangco and Frank A. Lattanzio and Stephen J. Beebe},
  journal={Cardiovascular Toxicology},
This study was designed to determine levels of NF-κB reporter gene activity and free radical generation in cultured striated myocytes (H9C2 cells) exposed to cocaine or morphine in the presence of free radical scavengers. Cells were transiently transfected with a NF-κB reporter gene and changes in luciferase activity were detected, by bioluminescence. Using confocal microscopy and 2′,7′-dichlorofluorescin diacetate, cocaine-induced or morphine-induced free radicals were quantified in H9C2 cells… 
Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling
Analysis of left-ventricular heart function in adult rabbits and gene expression microarray technology suggest that acute cocaine administration initiates cellular and genetic changes that could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling.
3,4-Methylenedioxymethamphetamine activates nuclear factor-κB, increases intracellular calcium, and modulates gene transcription in rat heart cells
Results suggest that MDMA may be toxic to the heart through its ability to activate the myocardial NF-κB response, disrupt cytosolic calcium and mitochondrial homeostasis, and alter gene transcription.
Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells
It can be concluded that morphine may protect H9c2 cells against oxidative stress and that this protection is at least partially mediated through activation of the p38 MAPK and PI3K/GSK-3β pathways.
Cocaine and human immunodeficiency virus type 1 gp120 mediate neurotoxicity through overlapping signaling pathways
Increased neurotoxicity mediated by cocaine and gp120 was ameliorated by NADPH oxidase inhibitor apocynin, thus underscores the role of oxidative stress, mitochondrial and MAPK signal pathways in cocaine and HIV gp120-mediated neurotoxicity.
3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function and Activates Nuclear Factor-Kappa B (NF-κB) in a Time and Dose Dependent Manner
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.
Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.
  • P. Kovacic
  • Chemistry, Biology
    Medical hypotheses
  • 2005


Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF‐kappa B transcription factor and HIV‐1.
It is shown that micromolar concentrations of H2O2 can induce the expression and replication of HIV‐1 in a human T cell line and suggests that diverse agents thought to activate NF‐kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI.
Signal Transduction of Opioid-induced Cardioprotection in Ischemia-Reperfusion
Stimulation of &dgr;1-opioid receptors generates oxygen radicals via mitochondrial KATP channels and this signaling pathway attenuates oxidant stress and cell death in cardiomyocytes.
Oxidant-induced activations of nuclear factor-kappa B and activator protein-1 in cardiac myocytes.
The findings suggest that altered expressions of cardiac genes regulated by AP-1 and NF-kappa B may be components of oxidant-induced injury to the heart or a part of the heart's adaptive response to oxidative stress.
Early activation of transcription factor NF-κB during ischemia in perfused rat heart.
The results suggest that early activation of NF-κB induced by ischemia in the myocardium could be a signal mechanism for controlling and regulating immediate-early gene expression during ischemIA-reperfusion.
Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes
Disruption of expression of VCAM-1 by inhibition of NF-κb activation may indicate a target for pharmacologic intervention intended to limit cardiac inflammation.
Rapid proteolysis of IκB-α is necessary for activation of transcription factor NF-κB
It is reported that IκB-α (formerly MAD-3)11 is degraded in cells after stimulation with phorbol ester, interleukin-1, lipopolysaccharide and tumour necrosis factor-α, an event coincident with the appearance of active NF-κB.
Enhancement of nitric oxide production by methylecgonidine in cultured neonatal rat cardiomyocytes
It is demonstrated that MEG significantly enhanced NO production in cultured cardiomyocytes and that the enhancement of NO production may result from MEG stimulation of muscarinic M2 receptors.
Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells
The data suggest that the death of cultured PC12 cells induced by the drugs of abuse is correlated with a decrease in intracellular dopamine levels, which can be associated with an increased dopamine turnover and oxidative cell injury.
Genetic toxicity of cocaine.
The data supports that cocaine could possess genotoxicity in addition to its well-known neurotoxicity and teratogenicity and the observation that non-toxic doses of cocaine can inhibit intercellular metabolic cooperation suggests that cocaine may also be a tumor promoter.