Doxorubicin‐Induced Cardiomyopathy in Children

Abstract

Doxorubicin-induced cardiotoxicity in childhood cancer survivors is a growing problem. The population of patients at risk for cardiovascular disease is steadily increasing, as five-year survival rates for all types of childhood cancers continue to improve. Doxorubicin affects the developing heart differently from the adult heart and in a subset of exposed patients, childhood exposure leads to late, irreversible cardiomyopathy. Notably, the prevalence of late-onset toxicity is increasing in parallel with improved survival. By the year 2020, it is estimated that there will be 500,000 childhood cancer survivors and over 50,000 of them will suffer from doxorubicin-induced cardiotoxicity. The majority of the research to-date, concentrated on childhood cancer survivors, has focused mostly on clinical outcomes through well-designed epidemiological and retrospective cohort studies. Preclinical studies have elucidated many of the cellular mechanisms that elicit acute toxicity in cardiomyocytes. However, more research is needed in the areas of early-and late-onset cardiotoxicity and more importantly improving the scientific understanding of how other cells present in the cardiac milieu are impacted by doxorubicin exposure. The overall goal of this review is to succinctly summarize the major clinical and preclinical studies focused on doxorubicin-induced cardiotoxicity. As the prevalence of patients affected by doxorubicin exposure continues to increase, it is imperative that the major gaps in existing research are identified and subsequently utilized to develop appropriate research priorities for the coming years. Well-designed preclinical research models will enhance our understanding of the pathophysiology of doxorubicin-induced cardiotoxicity and directly lead to better diagnosis, treatment, and prevention.

Protective Effect of Alamandine on Doxorubicin‑Induced Nephrotoxicity in Rats

“…This model was characterized by albuminuria, hypoalbuminemia, increased BUN and creatinine serum levels (two signi cant indicators of renal function), decreased creatinine clearance) indicator of GFR), associated with increased oxidative stress and in ammatory factors. The toxic effects of DOX administration observed in the current study are consistent with previous studies in which renal function parameters, including serum urea and creatinine, increased [19,20]. However, administration of almandine before, during and after doxorubicin injection was associated with improvement in renal function parameters through attenuated serum urea, creatinine, albumin, and creatinine clearance.…”

Effects of Cardiotoxins on Cardiac Stem and Progenitor Cell Populations

“…Loss of CSCs is unlikely to contribute to acute effects, excepting loss of CSC paracrine support for injured cells, but their contribution to angiogenesis could be linked to early- or late-onset chronic effects, respectively. The different rates of cardiotoxicity development in paediatric and adult patients are also notable ( 49 ), with cardiomyocyte apoptosis a feasible target for CSC-based protection and CSC protection against this already demonstrated ( 21 ).…”

Impact of corvitin and alpha-ketoglutarate on heart morphology, expression and activity of matrix metalloproteinases 2/9 in the heart of rats with doxorubicin-induced cardiomyopathy

“…The most common manifestations of the cardiotoxicity of doxorubicin are cardiac dysfunction and dilated cardiomyopathy. Moreover, the degree of damage to the heart depends on the dose and duration of doxorubicin administration (Chatterjee et al, 2010;Loncar-Turukalo et al, 2015;Mancilla et al, 2019). An application of this drug was also found to influence sensitivity of the heart to ischemic injury.…”