Effect of ICRF-187 pretreatment against doxorubicin-induced delayed cardiotoxicity in the rat

Morphological alterations induced by doxorubicin on H9c2 myoblasts: nuclear, mitochondrial, and cytoskeletal targets

“…It is pertinent to speculate that the same effects could be attained in vivo using a subchronic or chronic treatment with lower, pharmacological doses due to tissue drug accumulation. In fact, most alterations induced by Dox on H9c2 myoblasts, such as mitochondrial and nuclear damage, cytoplasm vacuolization, alterations in sarcomeric proteins, and apoptosis, are indeed observed in cardiac tissue after in vivo Dox treatment (Grimmond and Beerman 1982;Iwasaki and Suzuki 1991;Jang et al 2004;Jones et al 1990;Ueno et al 2006;Unverferth et al 1981;Villani et al 1990). …”

“…Contractile performance of atria is significantly reduced, accompanied by myocyte vacuolization and myofibrillar loss (Villani et al 1990). Endomyocardial biopsies performed in human hearts after Dox administration reveals an increase in sarcoplasmic reticulum and T-tubule size, again accompanied by cytoplasmic vacuolization.…”

“…However, clinical use of Dox is restrained by a chronic and cumulative cardiotoxicity that is manifested as a dilated congestive heart failure (Takemura and Fujiwara 2007). Impaired body weight gain and irreversible electrocardiogram alterations (prolongation of ST and QT intervals) are observed in rats 5 weeks after Dox administration (Villani et al 1990). Decrease in left ventricular developed pressure, increase in coronary perfusion pressure, ventricular fibrillation, shortening of ventricular action potential duration, reduction in cardiac index (cardiac output/body weight), and an increase in total peripheral resistance were some other parameters altered in rat and rabbit hearts in conjunction with morphological and biochemical alterations after Dox treatment (Joyeux et al 2001;Potemski et al 2006).…”

Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats

“…It has been documented that these ECG changes are associated with the prolongation of action potential duration and DOX could strongly affect the recovery phase of the transmembrane action potential, influencing preferentially Ca 2+ movements across the cellular membrane. 26,43,44 In addition, it has been reported that DOX alters calcium homeostasis in | 429…”

Doxorubicin-Induced Oxidative Injury of Cardiomyocytes - Do We Have Right Strategies for Prevention?

“…As a result, the pool of free iron in the myocardium is reduced and bound iron is displaced from its potentially damaging complexes with DOX, thus preventing the formation of superoxide radicals after redox recycling. DEX has been shown experimentally to reduce DOX-induced cardiotoxicity in mice (Alderton et al, 1990); in rats (Della Torre et al, 1999;Herman et al, 1994;Villani et al, 1990); in beagle dogs (Herman et al, 1988) and in miniature swine (Herman & Ferrans, 1983). Treatment with DEX not only significantly reduced the incidence of cardiac lesions, but also increased the survival rate in animals treated with anthracyclines compared with anthracycline-only treated controls.…”