Morphometric Characteristics Of The Mitochondrial Apparatus Of Cardiomyocytes At An Early Stage Of Chronic Doxorubicin-Induced Cardiomyopathy In Rats

Fiodarava E., Siamionik I.,  Archakova L.
Centre of electron and light microscopy, Institute of physiology of the National academy of science of Belarus, Minsk, Belarus

Toufik’s Medical Journal
Volume 1, Supplement 1, November 2021
Abstract from Biomedical Perspectives III 

Introduction: There is growing evidence that mitochondria play a central role in modulating doxorubicin (DOX)-induced cardiac failure. To assess the cardiotoxic effects of DOX, it is of great importance to elucidate the nature and severity of damage to the mitochondrial apparatus of cardiomyocytes (CMC) at an early stage of chronic DOXinduced cardiomyopathy (CMP) in rats.

Aim: The aim of his study was a morphometric analysis of the mitochondrial apparatus of CMC at an early stage of chronic DOX-induced CMP in rats. 

Materials and methods: The study was conducted on 20 white laboratory middle-aged rats: a control group and a group of animals with chronic CMP. The chronic CMP in rats was induced by DOX given at a cumulative dose of 16 mg/kg for 8 weeks. The animals were removed from the experiment on the 4th day after last administered dose of the medicine. An electron microscopic research method was used. Ultrastructural analysis was performed using a JEM-100 CX microscope, and morphometric evaluation was done using the ImageJ data processing software. The number of mitochondria, the ratio of total cross-sectional area of mitochondria to the total area of CMC, as a volume fraction of mitochondria in CMC (%), and the number of intermitochondrial contacts (IMC) per 100 mitochondria were evaluated. The Mann–Whitney’s test was used.

Results: A volume fraction of mitochondria in CMC decreased in experimental group of rats by 10,4% compared to the control group (32,27 [25,58;40,89] % versus 36,02 [32,35;40,12] %, р=0,07) on the 4th day after the simulation of chronic DOXinduced CMP. The number of mitochondrial profiles was by 8,1% higher than the control values (33,5 [29;46] versus (31 [28;34], p<0,05). The number of IMC decreased by 27,8% compared to control group (26 [24;33] versus 36 [34;41], p<0,01).

Conclusions: A mitochondrial hyperplasia with simultaneous loss of intermitochondrial contacts in rats was found at an early stage of chronic DOX-induced cardiomyopathy. These changes of mitochondria indicate the beginning depletion of energy and plastic reserves of myocardium.