Cardiomyocyte count in rat myocardium under the effect of antitumor agents cyclophosphamide and triterpenoids

Abstract

Structural reorganization of the myocardium in response to antitumor agents (cyclophosphamide, betulonic acid and its amide) was studied. Cardiotoxic effects of these chemicals manifested in cardiomyocyte contracture and lytic injuries and by significant hemodynamic disorders. The most pronounced lytic and necrobiotic changes in cardiomyocytes were detected after injection of cyclophosphamide followed by betulonic amide; this led to a more pronounced decrease in heart weight as a result of a decrease in total cardiomyocyte count. Antitumor drugs differently changed the ratio of mono- to binuclear cardiomyocytes, which differ by their regeneratory and compensatory adaptive potential.

Ultrastructural signs of cyclophosphamide-induced damage to cardiomyocytes

“…These data indicate that administration of CP is not followed by inhibition of intracellular regeneration in CMC. A decrease in the weight of the heart over the first 3 days after treatment is mainly related to the reduction of CMC [3].…”

“…Prodrug metabolism by cytochromes P450 results in the formation of bioactive substances with an unknown range of activity. Therefore, studying cardiotoxic activity of CP metabolites should include experimental evaluation of structural changes [3]. Little is known about the type of CP-induced ultrastructural changes in various cells (e.g., CMC).…”

Stimulation of Cardiomyocyte Regeneratory Reactions under Conditions of Cytopathic Hypercholesterolemia

“…Quantitative evaluation of the total cardiomyocyte population in the heart was carried out by alkaline dissociation of fi xed tissues [3,4]. In addition to the total cardiomyocyte count in the heart, the proportions of mono-, bi-, and multinuclear (with 3 and more nuclei) cardiomyocytes were evaluated.…”

Morphogenesis and Histostereological Analysis of Hepatopathy Induced by Cyclophosphamide

“…The resultant metabolites inhibit the growth of rapidly proliferating (primarily tumorous) cells. The absence of selective action and the uro-, nephro-, and cardiotoxicities of CP metabolites often become a serious problem in the clinical use of this drug [3].The hepatotoxic effects of CP remain an object of discussions. Some scientists think that the liver is least sensitive to toxicity of CP metabolites [8], while others claim that this organ is highly sensitive to the cytotoxic effect of CP [2].…”

“…The resultant metabolites inhibit the growth of rapidly proliferating (primarily tumorous) cells. The absence of selective action and the uro-, nephro-, and cardiotoxicities of CP metabolites often become a serious problem in the clinical use of this drug [3].…”