The study of the peculiarities of the adaptive-compensatory mechanisms of cardiomyocytes in the model of Alloxan induced diabetes in adult rats

Author: tornike leverashvili
Co-authors: M.Tokhishvili, N. Kharaishvili; M. tchanturia, N. Shavadze
Annotation:

In mammals, hepatocytes’ and cardiomyocytes’ ability of polyploidization is considered to be a protective evolutionary mechanism developed in response to variable environmental factors and stress (Ghiraldini et al., 2012). Polyploid cells are also formed in response to stress and various injuries. During apoptosis and oxidative stress-induced DNA damage, polyploid cells reproduce genetic material, conserve energy resources and maintain tissue functional activity (Celton-Morizur, et al., 2010). On the other hand, polyploidization of cardiomyocytes is considered to be a limiting factor for regeneration, because compared to normal diploid cells, high-ploidy cells have a low proliferation capacity (Patterson, M, Barske, L. 2017). An increase of ploidy in cardiomyocytes is shown after infarction, when the damaged areas of the ventricles experience compensatory hypertrophy due to increased functional load (Meckert, PC, Rivello, HG, 2005). Our work’s goal was to study the peculiarities of the adaptive-compensatory mechanisms of cardiomyocytes in the model of Alloxan induced diabetes in adult rats. At different time points (24h, 48h, 96h) after alloxan injection, no reliable quantitative changes of protein - NT-proBNP was detected in cardiomyocytes of adult rats. At the same time, there is no change in the areas of cardiomyocytes and their nuclei. At 24 h after Alloxan injection, the percentage of tetraploid (4C) cells is significantly increased, and the percentage of binucleated octaploid (4Cx2) and tetraploid (2Cx2) cells is decreased significantly compared to control group animals. At the 48th hour after Alloxan injection, the number of binuclear tetraploid (2Cx2) cardiomyocytes increases, while the number of binuclear octaploid (4Cx2) cells decreases. It should be noted that at the 96th hour the animals of the experimental group did not show any quantitative change in high ploidy cardiomyocytes. At 24 hours after Alloxan injection, immunohistochemical analysis of the tissue showed negative staining for TNF alpha. Compared to the control 48h after Alloxan injection, there is a trend of increased staining intensity for TNF alpha. At the 96th hour after the injection, the intensity of staining with antibodies against TNF-alpha increases visibly. It should be noted that the intensity is increased not homogeneously, but only in certain areas, which indicates the beginning of the development of cardiomyopathy. Conclusions: 1. At the initial stage of Alloxan induced diabetes, the change in the percentage ratio of high-ploid cardiomyocytes in the left ventricle of adult rat’s heart is mainly explained by the decrease in their part as a result of binuclear cardiomyocytes’ death. 2. At the early stage of Alloxan induced diabetes, the increased intensity of staining for antibodies to TNF alpha indicates the activation of the inflammatory process in response to the death of high-ploid cells in the organ.