A short review: Doxorubicin and its effect on cardiac proteins

Abstract

Doxorubicin (DOX) is a boon for cancer‐suffering patients. However, the undesirable effect on health on vital organs, especially the heart, is a limiting factor, resulting in an increased number of patients with cardiac dysfunction. The present review focuses on the contractile machinery and associated factors, which get affected due to DOX toxicity in chemo‐patients for which they are kept under life‐long investigation for cardiac function. DOX‐induced oxidative stress disrupts the integrity of cardiac contractile muscle proteins that alter the rhythmic mechanism and oxygen consumption rate of the heart. DOX is an oxidant and it is further discussed that oxidative stress prompts the damage of contractile components and associated factors, which include Ca2+ load through Ca2+ ATPase, SERCA, ryanodine receptor‐2, phospholamban, and calsequestrin, which ultimately results in left ventricular ejection and dilation. Based on data and evidence, the associated proteins can be considered as clinical markers to develop medications for patients. Even with the advancement of various diagnosing tools and modified drugs to mitigate DOX‐induced cardiotoxicity, the risk could not be surmounted with survivors of cancer.

Two-photon excitable membrane targeting polyphenolic carbon dots for long-term imaging and pH-responsive chemotherapeutic drug delivery for synergistic tumor therapy

“…Dox treatment had potential side effects, including cardiomyopathy, acute congestive heart failure (CHF), coronary artery syndrome, and arrhythmic conditions. 76 Therefore, excess RES trafficking of Dox may cause serious heart injuries apart from antitumor effects. 77 Our results indicate that the g -CQDs@Dox was accumulated in the liver after 1 h of administration, while the kidneys exhibited negligible accumulation of g -CQDs@Dox.…”

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

“…Overloading the mitochondria with calcium can result in mitochondrial malfunction and the induction of a cascade of pro-apoptotic events [74]. Furthermore, doxorubicin causes Ca 2+ -dependent Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activation as the result of promoting apoptosis [75].…”

MicroRNA in the Diagnosis and Treatment of Doxorubicin-Induced Cardiotoxicity

“…(5) Intracellular calcium dysregulation: during the metabolism of DOX, the toxic metabolite DOXOL is formed, which inhibits the sodium–calcium exchange channel, leading to an imbalance of calcium levels, an increase of intracellular calcium, and the production of ROS. In addition, CalcIUM/calmodulin-dependent protein kinase II (CaMKII) is a major Ca 2+ regulatory protein that can be oxidized and activated by free radicals, thus, further leading to an intracellular Ca 2+ imbalance [ 71 ]. This action can change the permeability of the cell’s membrane and mitochondria.…”