Mechanisms of tumor-associated cardiac muscle damage under different variants of melanoma growth

In case of the presence of a malignant process in an organism, the heart is subjected to an additional loading due to a unique combination of the external factors that is determined by the tumor biology and potentially cardiotoxic treatment actions and effects. It should be mentioned that cardiomyocytes have the same pathways of responding to stress and metabolic strategies as it is the case with the tumor cells, and this suggests that metabolic changes in the course of the tumor progression make their impact on the non-malignant tissue. Aim. The aim of our research work has been to study the level of the indices of the activity of free-radical processes and the hypoxia factor in cardiac mitochondria in mice under the different rates of the growth of B16 melanoma, growing either independently or against the background of chronic neurogenic pain. Materials and methods. In our experiment, we have used mice of both sexes of strain C57BL/6 (n = 56) and strain C57BL/6-Plautm1.1Bug - ThisPlauGFDhu/GFDhu (with uPA gene-knockout) (n = 56). We have composed the following experimental groups: an intact animal group (♂ n = 7; ♀ n = 7); a reference group (♂ n = 7, ♀ n = 7) with reproduction of the model of chronic neurogenic pain (CNP); a comparison group (♂ n = 63, ♀ n = 63) with a standard subcutaneous inoculation of melanoma (B16/F10), upon 2 weeks of the tumor growth; the main test group (♂ n = 63, ♀ n = 63) (CNP+B16/F10) with melanoma transplanted 3weeks after reproduction of the CNP model, with a tumor growing time of 2 weeks. After decapitation of the animals, the heart was harvested and mitochondria were isolated using the differential centrifugation with a highspeed refrigerated centrifuge. In the prepared mitochondria specimens with the use of ELISA assays we have determined concentrations of SOD 2 (pg/mg protein), GPx-1 (ng/mg protein), MDA mcM/g protein); AOPP (mcM/g protein); 8-hydroxy 2’ deoxyguanosine (8-OHdG) (ng/mg protein); the amount of protein (mg/mL) has been determined with a biochemical assay method, namely with the Biuret assay (Olvex Diagnosticum, Russia). The obtained statistics data have been processed with software Statistica 10.0. Results. In the female mice of strain C57BL/6, when comparing the studied data in cardiac mitochondria between the groups with the independent growth of melanoma and that in combination with CNP, we have revealed the higher levels of MDA increased by a factor of 1,8 (p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }