Actions and effects of malignant tumor growth and chronic neurogenic pain exerted on the glutathione system in cardiac mitochondria in experimental animals
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The aim hereof is to study the glutathione system peculiarities in the cardiac mitochondria in experimental animals against the background of a tumor process, chronic pain and the combined effect both of chronic pain and the tumor process.
Materials and methods
The experiment has been carried out in female mice of the C57BL / 6 line (n = 28), aged 8 weeks, with an initial body mass of 21-22 g. The animals have been divided into the following groups: an intact group as the reference (n = 7), a test group with a reproduction of the chronic pain model (n = 7), a comparison test group (B16/F10), which covered the animals with standard subcutaneously inoculated melanoma B16/F10 (n = 7), and the main experimental group (chronic pain + B16/F10) of mice with B16/F10 melanoma inoculated 3 weeks after the chronic pain model development (n = 7). All rodents have been decapitated with a guillotine upon completion of 3 weeks of the experiment (on 21 day of the experiment). After decapitation, the animal hearts have been quickly removed with the use of coolants, and mitochondria have been isolated. In the obtained mitochondrial samples, using standard IFA test systems, the following levels have been determined: reduced glutathione (GSH) in nmol/L , oxidized glutathione (GSSG) in nmol/L, glutathione peroxidase-1 (GPx-1) in ng/mL, glutathione peroxidase-4 (GPx-4) in ng/mL, glutathione reductase (GR) in ng/ mL, glutathione -S- transferase (GST) in ng/mL and superoxide dismutase-2 (SOD-2) in pg/mL. The statistics data have been calculated using the Statistica 6.0 software.
In case of a chronic pain and a tumor process, in the cardiac mitochondria a low concentration of GPx-1, SOD-2 and a high level of GSSG are detected. The amount of GR increases in case of chronic pain and decreases under a malignant process. The combined effect of a chronic pain and a malignant process leads to a decrease in GSH against the background of an elevated GSSG level. The enzymatic component of the glutathione system (GPx-1, GR, GST) in the cardiac mitochondria in case of the combined actions and effects is characterized by a cumulative potential. The GSH/GSSG ratio in all experimental groups is statistically significantly lower than the intact values.
According to the results from this study, we may conclude that chronic pain and a tumor process exert systemically an effect on the animal's organism, but in doing so they affect different members of the regulation in the LPO-AOP system. A disorder in the glutathione system performance triggers an activation of molecular oxygen and a change in the redox potential that in its turn affects the subcellular level of the regulation and, in general, the entire cellular metabolism. The revealed abnormalities in the energy system of the cardiac mitochondria can be considered as stressor disorders. The combined effect of a chronic pain and a malignant process is treated by the organism as a double stress with an imbalance in the antioxidant glutathione system.
Irina V. Neskubina, Elena М. Frantsiyants, Ekaterina I. Surikova, Irina V. Kaplieva, Lyubov К. Trepitaki, Lyudmila А. Nemashkalova, Yulia A. Pogorelova, Alla I. Shikhlyarova, Galina V. Zhukova, Pavel N. Anistratov, Viktoria L. Volkova, Natalia А. Chertova, Oksana Е. Zhenilo, Anna А. Cherkasova, Olga G. Selezneva. Actions and effects of malignant tumor growth and chronic neurogenic pain exerted on the glutathione system in cardiac mitochondria in experimental animals. Cardiometry; Issue 13; November 2018; p.27-34; DOI: 10.12710/cardiometry.2018.13. 2734; Available from: http://www.cardiometry.net/issues/no13-november-2018/glutathione-system-in-cardiac-mitochondria