Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

Abstract

Today the pharmacological possibilities of treating cancer are expanding and as a result, life expectancy is increasing against the background of chemotherapy and supportive treatment. In the conditions of successful antitumor treatment, complications associated with its toxic effect on healthy tissues and organs began to come to the fore. Anthracycline cardiomyopathy was the first serious cardiovascular complication to draw the attention of oncologists and cardiologists around the world. Anthracycline drugs such as doxorubicin, epirubicin, idarubicin are still widely used in oncological practice to treat a wide range of solid and hematological malignancies. Doxorubicin-induced cardiomyopathy is closely associated with an increase in oxidative stress, as evidenced by reactive oxygen species (ROS) nduced damage such as lipid peroxidation, and decreased levels of antioxidants. Myofibrillar destruction and dysregulation of intracellular calcium are also important mechanisms, usually associated with doxorubicin-induced cardiotoxicity. Despite the abundance of data on various mechanisms involved in the implementation of doxorubicin-induced cardiotoxicity, a final understanding of the mechanism of the development of doxorubicin cardiomyopathy has not yet been formed. It poses the most significant challenges to the development of new methods of prevention and treatment, as well as to the unambiguous choice of a specific treatment regimen using the existing pharmacological tools. In order to resolve these issues new models that could reflect the development of the chemotherapy drugs effects are needed. In this review we have summarized and analyzed information on the main existing models of doxorubicin cardiomyopathy using small laboratory animals. In addition, this paper discusses further areas of research devoted to the development and validation of new improved models of doxorubicin cardiomyopathy suitable both for studying the mechanisms of its implementation and for the preclinical drugs effectiveness assessment.

Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study

“…It has been shown that DOX-induced oxidative damage is associated with acute toxicity that induced by single dose of DOX in animals [ 40 , 41 ]. Furthermore, it has been reported that DOX toxicity can be divided into three categories: acute, subacute, and chronic toxicity [ 42 , 43 ]. Acute toxicity (short-term model) is induced following a single dose of DOX (dose usually ranges from approximately 5–30 mg/kg) and can lead to liver, renal, and cardiac damage.…”

Anticancer Drug-Induced Cardiotoxicity: Insights and Pharmacogenetics

“…It is a highly successful chemotherapeutic medication for solid tumors, soft-tissue sarcoma, breast cancer, Hodgkin’s disease, Kaposi’s sarcoma, acute lymphoblastic leukemia, pediatric leukemia, lung cancer, lymphomas, and various metastatic malignancies [ 2 , 38 , 39 ]. The drug’s utility is limited owing to its large number of side effects, such as the suppression of the hematopoietic system, gastrointestinal disturbances, and baldness, with cardiac damage being the most dangerous [ 40 , 41 , 42 ].…”

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects

“…The mechanisms of anthracycline cardiotoxicity are still being investigated in various experimental models [5]. All anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) have a general mode of ultrastructural myocardial damage, which is characterized by loss of myofibrils, expansion of the sarcoplasmic reticulum, cytoplasmic vacuolization, swelling of mitochondria and an increase in the number of lysosomes [9].…”

“…Cardiotoxicity is dose-dependent and can develop during or immediately after the administration of doxorubicin, as well as some time after the end of treatment. Thus, acute and chronic doxorubicin cardiotoxicity is separated [4,5].…”