Acute Cardiotoxic Effects of Adjuvant Trastuzumab Treatment and Its Relation to Oxidative Stress

Abstract

Our aim was to evaluate the acute cardiac toxicity of adjuvant trastuzumab treatment and its possible relation to changes in oxidative stress. Electrocardiographic and echocardiographic tissue Doppler imaging (TDI) parameters, activity of antioxidant enzymes (superoxide dismutase; SOD), and products of oxidative stress (malondialdehyde; MDA) were analyzed in 30 patients with early-stage breast cancer who had adjuvant trastuzumab treatment. There was a significant prolongation of QT interval after trastuzumab treatment. There was also a significant decrease in left ventricular ejection fraction (LVEF), TDI-derived S' parameters, and SOD enzyme activity and increase in MDA levels after trastuzumab infusion. There was a positive correlation between changes in SOD activity and LVEF and a negative correlation between changes in MDA levels and LVEF. This study demonstrated a correlation between decreases in LVEF and increases in products of the oxidative stress in patients who had adjuvant trastuzumab treatment.

Cardiovascular Toxicity Induced by Kinase Inhibitors: Mechanisms and Preclinical Approaches

“…Vemurafenib, a selective BRAF inhibitor, was also associated with an increased in QT interval in 7–10% of patients . Trastuzumab, a monoclonal antibody that binds to the extracellular domain of HER2, resulted in CV effects including QT prolongation . Accordingly, many of these drugs have warnings for acquired QT prolongation on their labels.…”

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity

“…Similarly, TZM also binds to HER-2 and increases proapoptotic Bcl-xS expression while it decreases antiapoptotic Bcl-xL expression (Grazette et al, 2004;Sadek et al, 2017). These result in overwhelming ROS production and reduced ROS scavenging activities with consequent profound inhibition of SOD, CAT, GST, and GPx activities, reduced GSH levels as well as increased MDA levels of TZM-treated tissues (Dirican et al, 2014). The fact that the referred cardiac oxidative stress enzyme activities were profoundly inhibited by the TZM treatment, our finding is, thus, in tandem with other earlier findings (Dirican et al, 2014;Teppo et al, 2017;Gorini et al, 2018).…”

“…These result in overwhelming ROS production and reduced ROS scavenging activities with consequent profound inhibition of SOD, CAT, GST, and GPx activities, reduced GSH levels as well as increased MDA levels of TZM-treated tissues (Dirican et al, 2014). The fact that the referred cardiac oxidative stress enzyme activities were profoundly inhibited by the TZM treatment, our finding is, thus, in tandem with other earlier findings (Dirican et al, 2014;Teppo et al, 2017;Gorini et al, 2018). Also, the fact that VAL, LSP, ADP and their fixed-dose combinations profoundly improved the activities of oxidative stress marker enzymes in the treated rats strongly suggest the protective role of these antihypertensive agents in TZM-induced tissue oxidative stress mediated via reduced caspase-3 and caspase-9 production as well as increased antioxidant mechanisms.…”

Danshenol A Alleviates Hypertension-Induced Cardiac Remodeling by Ameliorating Mitochondrial Dysfunction and Suppressing Reactive Oxygen Species Production

“…Growing evidence indicates that ROS is essential for the pathogenesis of cardiac remodeling, which may also exert an obvious effect in the progression from pathological remodeling to heart failure [26, 27]. For example, Dirican et al reported a negative relevant relation between MDA and LVEF [28]. Yokota et al found that the activation of SOD, catalase, and GSHIPx did not decrease in failing hearts, which indicated that oxidative stress in heart failure is mainly owing to the increase of prooxidant generation rather than to the reduction of antioxidant defenses [29].…”