Functional state of cardiomyocyte mitochondria in malignant process in presence of comorbid pathology in experiment
Purpose of the study. An analysis of indices of free radical oxidation and respiration of mitochondria of heart cells in a malignant process in presence of diabetes mellitus and chronic neurogenic pain in experimental animals. Materials and methods. The study included outbred female rats ( n= 32) and С57ВL/6 female mice ( n= 84). Experimental groups of rats were: intact group 1 ( n= 8), control group 1 ( n= 8) with diabetes mellitus (DM), comparison group 1 ( n= 8) with standard subcutaneous transplantation of Guerin's carcinoma, main group 1 ( n= 8) with Guerin's carcinoma transplanted after 1 week of persistent hyperglycemia. Experimental groups of mice were: intact group 2 ( n= 21), control group 2 ( n= 21) with a model of chronic neurogenic pain (CNP), comparison group 2 ( n= 21) with standard subcutaneous transplantation of melanoma (B16/F10), main group 2 ( n= 21) (CNP+B16/F10) with melanoma transplanted 3 weeks after the CNP model creation. Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/mg of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/mg of protein), and malondialdehyde (MDA) (μmol/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program. Results. DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times ( р= 0.0000) and downregulated cytochrome C by 1.5 times ( р= 0.0053) in heart cell mitochondria, compared to intact values. DM+Guerin's carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times ( р= 0.0000) and decreased cytochrome C by 1.5 times ( р= 0.0000), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times ( р= 0.0000) and decreased cytochrome C by 1.6 times ( р= 0.0008). Conclusions. Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells with destabilization of the respiratory chain mediated by free radical oxidation processes.