The role of doxorubicin in the formation of cardiotoxicity is a consensus statement. Part II. Cardiotoxicity of doxorubicin unrelated to myocytes and cardioprotection strategy (review)

Abstract

Introduction. The use of doxorubicin in clinical practice has shown cumulative and dose-dependent toxic effects on cardiomyocytes, leading to an increase of mortality risk among patients with cancer and as a resulting to restrictions in the indications for its use.Text. A dangerous adverse reaction of doxorubicin is cardiomyopathy, leading to congestive heart failure. Cardiotoxicity is based on at least several pathophysiological mechanisms (described in more detail in the first part of the review), leading to damage to cardiomyocytes as a result of oxidative stress with the formation of free radicals, dysfunction of mitochondria, autophagy, release of nitric oxide and inflammatory mediators, as well as changes in gene expression and proteins leading to apoptosis. The current (second) part of the review provides detailed information on the actual understanding of the pathophysiological mechanisms underlying the described cardiotoxicity, the effect of doxorubicin on other heart cells. The use of cardioprotective strategies will reduce the severity and likelihood of developing cardiotoxicity. This article describes strategies based on reducing the maximum cumulative dose, changing the speed of doxorubicin administration, using pegylated liposomal formulations and cardioprotective agents, as well as exercise.Conclusion. Despite the huge number of scientific papers devoted to various aspects of cardiotoxicity of doxorubicin, its prevention and treatment, this issue requires more careful study and development of more advanced methods of early diagnosis, prevention and more effective therapy the complication.

Keywords

• anthracycline chemotherapy drug
• doxorubicin
• cardiotoxicity
• cardiomyocytes
• mitochondria