State of free-radical processes in the heart cell mitochondria under melanoma В16/F10 growth against the background of chronic neurogenic pain as comorbid pathology
* Corresponding author
The aim hereof has been to investigate the dynamics of processes of free radical oxidation and antioxidant protection in the heart cell mitochondria in female mice of strain С57ВL/6 at different stages of the В16/F10 melanoma growth under the comorbid pathology conditions, namely, chronic neurogenic pain.
Materials and methods
Our research work was conducted in female mice of strain С57ВL/6 (n=168). The animals were randomly distributed in separate groups as follows: the group of intact mice (n=21); the reference group (RCNP) (n=21) to reproduce the model of chronic neurogenic pain (CNP); group M (n=63) with melanoma B16/F10 upon subcutaneous transplantation of the tumor; group CNP + M (n=63), where the В16/F10 melanoma was transplanted 3 weeks after CNP modeling. In the heart cell mitochondria samples, using ELISA tests, we have determined concentrations of superoxide dismutase 2 (SOD 2) (pg/mg protein), 8-hydroxy 2’ deoxyguanosine (8-OHdG) (ng/mg protein); malone dialdehyde (MDA) (mcM/mg protein); the total SOD activity (units/mg protein), the Mn SOD activity (units/mg protein) and the Cu-Zn SOD activity (units/mg protein). The obtained statistics data have been processed with software Statistica 10.0.
Under the CNP conditions, we have revealed in the female mice in the heart cell mitochondria that the SOD 2 level has decreased by 2,9 times, the total SOD activity has been diminished by 1,54 times (р<0,05), and the Cu-ZN SOD activity has been recorded to be 2,7 times lower, as compared with the respective data in the intact animals. 1 week after the melanoma growth stimulated by CNP, as against the reference values, an increase in the SOD 2 level by 3,2 times has been identified, and it has demonstrated high values upon expiration of 2 and 3 weeks of the tumor growth. Considering the same period of the tumor growth under the CHP conditions, we have observed an elevation of the activity of the total SOD and the Mn SOD by 1,7 and 2 times, respectively (р<0,05). On the contrary, 1 week after the stimulated tumor growth, the Cu-Zn SOD activity has been lowered reaching its undetectable values; upon expiration of 2 weeks it has been found to be at the level of the respective reference values, but after 3 weeks its decrease by 3 times has been recorded. The 8-OHdG concentration has been revealed to be increased after 1 week by 4 times and after 2 weeks by 6,6 times, respectively. The MDA level in week 1 and 2 has exceeded the reference levels on the average by 2 times. Upon expiration of 3 weeks of the stimulated tumor growth, both indicators have been found to reach the level of the reference values.
The accompanying chronic neurogenic pain has contributed to the functional re-setting of subcellular structures in the organs not affected by the tumor. In the heart cell mitochondria, which are considered as the most sensitive mechanisms in the cell regulation, we can observe surges in the prooxidant activity followed by further dynamics of its normalization. The initial suppression of the activity of the antioxidant system elements gives the way to a considerable surge and maintenance of a permanent or a variable high level of the activity that bears witness to the fact that stress or tension develops accompanied by depletion of energy resources of the heart under the CNP conditions.
Elena M. Frantsiyants, Irina V. Neskubina, Alla I. Shikhlyarova , Ekaterina I. Surikova, Lidia K. Trepitaki, Lyudmila A. Nemashkalova, Valerija A. Bandovkina, Irina V. Kaplieva, Lyudmila Y. Rozenko, Sergey N. Dimitriadi. State of free-radical processes in the heart cell mitochondria under melanoma В16/F10 growth against the background of chronic neurogenic pain as comorbid pathology. Cardiometry; Issue 18; May 2021; p.131-137; DOI: 10.18137/cardiometry.2021.18.131137; Available from: http://www.cardiometry.net/issues/no18-may-2021/free-radical-processes