The cardiotoxic antibiotic doxorubicin inhibits the Na⁺/Ca²⁺ exchange of dog heart sarcolemmal vesicles

Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+increase are reciprocally modulated in rat cardiomyocytes

“…In this study, the molecular basis of DOX-induced intracellular Ca 2+ regulation has been examined (Keung et al, 1991), inhibits Na + -Ca 2+ exchanger (Caroni et al, 1981), or releases Ca 2+ from SR (Zorzato et al, 1985;Kim et al, 1989). Our results have shown that DOX-mediated increase of [Ca 2+ ]i is due to a release of Ca 2+ from SR through ROS-mediated opening of RyR.…”

“…Direct effects of the drug on various Ca 2+ channels have also been observed. DOX increases the open probability of sarcoplasmic reticulum (SR) calcium release channels (Zorzato et al, 1985;Kim et al, 1989), inhibits Na + -Ca 2+ exchanger (Caroni et al, 1981) or activates L-type cardiac calcium channel (Keung et al, 1991). All of these DOX effects on Ca 2+ channels can lead to Ca 2+ overload of cardiac cells that may render mitochondrial calcium overloading, resulting in alteration of energy metabolism and generation of reactive oxygen species (ROS).…”

A Calcium Antagonist Protects against Doxorubicin-Induced Impairment of Calcium Handling in Neonatal Rat Cardiac Myocytes

“…Inhibition of the Na + -Ca 2+ exchanger in isolated dog heart sarcolemmal vesicles 10 and of the Ca 2+ pump of the canine cardiac SR 11 by DOX have been reported. These mechanisms may be responsible for the impairment of removal of intracellular free calcium ion in the contraction-relaxation cycles in this study.…”

Doxorubicin Cardiotoxicity

“…29 Another report has also shown that DOX inhibits the Ca 2+ pump of the canine cardiac SR. 30 The reduction in ATP levels of myocytes caused by impaired mitochondrial oxidative function, 31 which may impair the calcium uptake by the SR, and this may also account for the abnormal sequestration of intracellular free calcium ions. Lee et al 18 reported that a low cumulative dose of DOX (193 mg/m 2 ) decreased diastolic function (decreased left ventricular filling velocity) without decrease in contractile function in patients.…”