Metabolomic Perspectives in Antiblastic Cardiotoxicity and Cardioprotection

Abstract

Despite advances in supportive and protective therapy for myocardial function, cardiovascular diseases due to antineoplastic therapy—primarily cardiomyopathy associated with contractile dysfunction—remain a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators are searching for alternative strategies that can timely recognise cardiovascular damage—thus permitting a quick therapeutic approach—or prevent the development of the disease. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as tyrosine kinase inhibitors. In recent years, metabolomics has proved to be a practical tool to highlight fundamental changes in the metabolic state in several pathological conditions. In this article, we present the state-of-the-art technology with regard to the metabolic mechanisms underlying cardiotoxicity and cardioprotection.

A Comparative Study of Rat Urine 1H-NMR Metabolome Changes Presumably Arising from Isoproterenol-Induced Heart Necrosis Versus Clarithromycin-Induced QT Interval Prolongation

“…This altered TCA cycle activity could be linked to an ongoing heart necrosis process or even organ failure [38][39][40]. Li et al also highlighted metabolic changes in serum of rats exposed to ISO suggesting an early alteration of heart mitochondrial energy metabolism, using UPLC-Q-TOF-MS [22]. Some evidence suggests that the cardiotoxicity of many drugs is related, at least partially, to a mitochondrial deficiency.…”

“…Early works studied hepatic and renal toxicities in order to characterize their metabolic signatures helping the discovery of new predictive biomarkers [14,19,20]. In the past decade, some metabonomic works began to focus on drug-induced cardiotoxicity, mainly using serum and heart tissue extracts as investigative matrices [21,22]. Those works opened the way to consider metabonomics as a promising approach to discover specific biomarkers of cardiotoxicity.…”

Prognostic Factors for Cardiotoxicity Among Children With Cancer: Definition, Causes and Diagnosis With Omics Technologies

“…On the other hand, the most important advantage of mass spectrometry coupled with upfront chromatography is of far greater sensitivity than NMR MS-based systems that have been used to resolve compounds in the nanomole to picomole and even femtomole range, whereas identification of compounds by 1H-NMR requires concentrations of 1 nanomole or higher. [96][97] The main methodologies that are used for metabolomic analysis are untargeted and targeted metabolomics. Untargeted metabolomics allow measuring a wider variety of metabolites present in an extracted sample without prior knowledge of the metabolome.…”

Metabonomics Analysis of Myocardial Metabolic Dysfunction in Patients with Cardiac Natriuretic Peptide Resistance

“…Metabolic dysregulation is one of the important components of the complex pathogenesis of HF [ 16 – 18 ]. Metabolic perturbation in HF is not just a disorder of the myocardium but also a systemic problem because changes in the composition of metabolites in circulation reflect the overall and systemic pathological changes, which is occurring in the failing heart along with changes in multiple organs and tissues throughout the body [ 19 – 22 ].…”