Abstract
Along with a good antitumor effect, Doxorubicin has a systemic effect with damage to vital organs, in particular the heart. The lack of a unified approach to dosing and the frequency of administration of Doxorubicin in the experiment prompts the search for an optimal model of Doxorubicin cardiomyopathy. The aim of the study was to develop a method of serial administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received systemic chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th, the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysia). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During systemic chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data indicate the development of dilated cardiomyopathy in experimental animals. Serial intraperitoneal administration of Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks causes morphological changes in the myocardium of experimental animals, similar to changes in the heart of people undergoing chemotherapy with this drug.
Highlights
Despite constant scientific and technological progress, the incidence and mortality from cancer are increasing rapidly worldwide [5, 18].Cancer treatments include surgery, radiation therapy, and systemic treatment, which includes chemotherapy, targeted therapy, hormone therapy, and immunotherapy [5]
The aim of the study was to develop a method of serial administration of Doxorubicin in moderate therapeutic doses in the experiment and to evaluate the cardiotoxic effect of the drug
The experimental group consisted of 35 rats, which underwent systemic chemotherapy with Doxorubicin according to the author's method (Patent of Ukraine for utility model No 138091 from 25.11.2019)
Summary
Radiation therapy, and systemic treatment, which includes chemotherapy, targeted therapy, hormone therapy, and immunotherapy [5]. Pharmacological drugs are the most common means of influencing tumor growth and metastasis and are used in almost all malignant cancers, even in the early stages [6, 8, 9, 10, 11, 22, 23]. Chemotherapeutics creates a systemic toxic effect, which is one of the most significant disadvantages of the use of chemotherapeutics, and even with local administration of drugs [16, 27]. The list of cardiotoxic therapeutic agents against cancer includes anthracyclines, trastuzumab, alkylating agents, antimetabolites, tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors and proteasome inhibitors [1, 4, 12]
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