scholarly journals Influence of B16/F10 melanoma growth variant on calcium levels in mitochondria in various organs of female mice

2021 ◽  
Vol 8 (1) ◽  
pp. 20-29
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
E. I. Surikova ◽  
I. V. Kaplieva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Pain Syndrome ◽  
Neurogenic Pain ◽  
Intact Group ◽  
Female Mice ◽  
Terminal Stage ◽  
Initial Stage ◽  
The Brain ◽  
Melanoma Growth

Purpose of the study. To analyze the calcium levels in mitochondria of cells in different organs in standard and stimulated growth of experimental В16/F10 melanoma. Materials and Methods. The study included female С57ВL/6 mice (n=168). Experimental groups: intact group (n=21), group with a model of chronic neurogenic pain (CNP) (n=21), group M – B16/F10 melanoma (n=63), group M+CNP – mice (n=63) with transplantation of B16/F10 melanoma 3 weeks after CNP model creation. The concentration of calcium in mitochondrial samples was determined by a biochemical method (Abris+, Russia). Results were statistically analyzed using the Statistica 10.0 program. Results. CNP decreased calcium levels in mitochondria of cells in the brain by 1.4 (р=0.00153) times, liver by 2.6 times and heart by 3.2 times and increased the levels in the skin by 97.1 times. In standard growth of experimental melanoma, levels of calcium in cell mitochondria in most of the studied organs increased at the initial stage of the melanoma growth, and decreased to intact values and lower by the terminal stage. In the mitochondria of tumor cells, calcium levels were stably high at all stages of standard tumor growth. At the initial stage of CNP‑stimulated tumor growth, a decrease in calcium in the mitochondria of the skin by 5.7 times and its accumulation in the mitochondria of the brain by 6.6 times, heart, and kidneys were recorded by 1.5 times. At the terminal stage of stimulated melanoma growth, extremely low calcium values were recorded in the mitochondria of all organs. A stably low level of calcium was registered in the mitochondria of tumor cells at all stages of stimulated melanoma growth. Conclusions. The growth of experimental B16/F10 melanoma in female mice is accompanied by mitochondrial dysfunction affecting most organs. Stimulation of the growth of experimental melanoma with chronic neurogenic pain, unlike the standard growth variant, changes accumulation of calcium in the mitochondria of cells both in organs and in the tumor itself. The chronic pain syndrome accompanying a malignant process can influence its course with the involvement of mitochondria and the modification of their functions.

Aminergic status in the brain of urokinase gene-deficient mice with malignant tumors growing in presence of chronic neurogenic pain.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21582-e21582
Author(s):  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Elena M. Frantsiyants ◽  
Ekaterina I. Surikova ◽  
Valeria A. Bandovkina ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Tumor Growth ◽  
Biogenic Amines ◽  
Malignant Tumors ◽  
Gene Knockout ◽  
Significant Inhibition ◽  
Mouse Strains ◽  
Neurogenic Pain ◽  
The Brain ◽  
Melanoma Growth

e21582 Background: The fibrinolytic system of the brain is important for its normal functioning and participation in processes that are significant in various stressful influences, including tumor growth and chronic neurogenic pain (CNP). These pathological conditions change the activity of the brain neurotransmitter system. On the other hand, urokinase deficiency is associated with significant inhibition of tumor growth, while CNP – with its stimulation. The purpose of the study was to analyze the effect of CNP on the levels of biogenic amines in the brain of mice with urokinase deficiency (uPA-/-) with transplanted B16/F10 melanoma. Methods: The study included male and female mice: С57ВL/6 (uPA+/+, n = 48) and C57BL/6-Plautm1.1Bug-ThisPlauGFDhu/GFDhu (urokinase gene-knockout - uPA-/-, n = 48). Mouse strains were divided into subgroups (each n = 6): intact; with CNP (bilateral sciatic nerve ligation); 21 days after subcutaneous transplantation of B16/F10 melanoma; 21 days of B16/F10 melanoma growth in presence of CNP (B16/F10+CNP), with tumor transplantation 2 weeks after the sciatic nerve ligation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine, serotonin (5HT), and 5-hydroxyindoleacetic acid (5OHIA) were determined in the brain by ELISA (Cusabio, China). Statistical processing - Statistica 10.0. Results: Levels of NA, DA and 5HT in the brain of intact uPA-/- mice were 3.5, 2.1 and 1.9 times higher (p < 0.05), respectively, than in intact uPA+/+ animals, while histamine and 5OHIA were on average 2.0 times lower. The dynamics of cerebral levels of biogenic amines in uPA-/- mice with pathological factors, alone or combined, had practically no gender specificity, with rare exceptions. So, 5HT levels increased up to 4.5 times in uPA-/- mice of both sexes in response to CNP or B16/F10 growth. Melanoma growth in presence of CNP, on the contrary, decreased 5HT by 3-10 times and DA by 1.6 times (p < 0.05) both in males and females, and decreased NA by 1.6 times (p < 0.05) in females. Conclusions: CNP together with melanoma inhibits the initial activation of the HA-, DA- and 5HT-ergic systems in the brain of uPA-/- mice, which may be an important pathogenetic mechanism of the cancellation of genetically determined inhibition of subcutaneous B16/F10 melanoma growth in urokinase deficiency.

scholarly journals Influence of a B16/F10 melanoma variant on the Вcl-2 levels in mitochondria in various organs of female mice

2021 ◽  
Vol 20 (3) ◽  
pp. 46-53
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
N. D. Cheryarina ◽  
A. I. Shikhlyarova ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Development ◽  
Growth Period ◽  
Pathological Process ◽  
Intact Group ◽  
Kidney Mitochondria ◽  
Female Mice ◽  
Thermo Fisher Scientific ◽  
Liver And Kidney ◽  
Melanoma Growth

Aim. To study the Bcl-2 level in mitochondria of various organs in female mice with standard and stimulated growth of an experimental B16/F10 melanoma.Materials and methods. The study included С57ВL/6 female mice (n = 168). The experimental animals were divided into the following groups: an intact group (n = 21), a group with modelled chronic neuropathic pain (CNP) (n = 21), an M group with B16/F10 melanoma (n = 63), and a CNP + M group (n = 63). The Bcl-2 concentration (ng / mg protein) in mitochondrial samples was determined by ELISA (Thermo Fisher Scientific, Austria). Statistical analysis of the results was carried out using Statistica 10.0.Results. Compared to the Bcl-2 levels in the intact animals, CNP decreased this parameter in the cardiac mitochondria by 1.3 times, while increasing it by 5.9 times in the skin mitochondria. In the dynamics of standard melanoma growth, the Bcl-2 content changed compared with the corresponding intact values in the mitochondria of the brain, heart, and skin, but did not change in the liver and kidneys. In the mitochondria in melanoma, the Bcl-2 levels were high throughout the entire period of standard tumor growth in comparison with the intact skin. The stimulated melanoma growth in CNP was involving more organs into the pathological process as the tumor was growing. Thus, in comparison with the values in the CNP group, the mitochondrial Bcl-2 levels changed in the heart at week 1; in the heart and skin – at week 2; in the heart, skin, and brain – at week 3. The Bcl-2 levels did not change in the liver and kidney mitochondria. In the mitochondria in the CNP-stimulated melanoma, the Bcl-2 levels were lower than in the skin mitochondria in CNP throughout the entire tumor growth period.Conclusion. The liver and kidney mitochondria are somewhat Bcl-2 stable in both standard and stimulated tumor growth. It is assumed that different Bcl-2 dynamics in the mitochondria in melanoma depending on the variant of tumor development reflects the modulating effect of CNP and the ability to change the Bcl-2 levels according to the growth phase.

scholarly journals Influence of B16/F10 melanoma growth variant on the level of cytochrome C in mitochondria in various organs of female mice

2021 ◽  
Vol 27 (4) ◽  
pp. 46-52
Author(s):  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
N. D. Cheryarina ◽  
E. I. Surikova ◽  
L. A. Nemashkalova
Keyword(s):  
Statistical Analysis ◽  
Cytochrome C ◽  
Complex Iii ◽  
Neurogenic Pain ◽  
Complex Iv ◽  
Female Mice ◽  
Slowing Down ◽  
Analysis Of Results ◽  
The Brain ◽  
Melanoma Growth

Introduction. Cytochrome C in mitochondria transfers electrons from complex III to complex IV, and it is a signaling molecule in the apoptosis realization.The objective was to evaluate the level of cytochrome C in cell mitochondria in various organs of female mice with standard and stimulated growth of experimental B16/F10 melanoma.Methods and materials. The experiment was performed on female C57BL/6 mice (n=168). The groups were: intact animals (n=21); controls with a model of chronic neurogenic pain (CNP) (n = 21); group M — standard B16/F10 melanoma transplantation (n=63), group CNP + M — B16/F10 melanoma transplantation 3 weeks after CNP model creation (n=63). The level of cytochrome C (ng / mg protein) were measured by ELISA (Bioscience, Austria). Statistical analysis of results was performed using the «Statistica 10.0» program.Results. After 1 week of standard melanoma growth, an increase in the level of cytochrome C by 2.7 and 1.7 times was detected in mitochondria of the brain and liver; by the 3rd week, it decreased in the liver and skin by 1.7 times. In melanoma mitochondria, the level of cytochrome C was lower than in the skin of intact animals: by 2.5 times after week 1, by 4.5 times after week 2, and by 4.6 times after week 3. After 1 week of stimulated melanoma growth, the level of cytochrome C decreased compared control values: by 2.2 times in the brain, by 1.9 times in the liver, by 1.4 times in the skin; by week 3, it decreased by 4.8 times in mitochondria of the brain, by 4.7 times — in the liver, by 2.3 times — in the heart, by 1.9 times — in the skin. In melanoma mitochondria, the level of cytochrome C was lower than in the skin of intact animals: by 15.3 times after week 1, by 10.3 times after week 2, and by 8.8 times after week 3.Conclusion. Low level of cytochrome C were found in melanoma mitochondria in standard and stimulated tumor growth. The data can be used in the experiment and in clinic for using exogenous cytochrome C as an agent slowing down the malignant process.

scholarly journals The state of apoptosis factor system in mitochondria of skin and tumor cells in standard and stimulated growth of B16/F10 melanoma in female C57BL/6 mice

2021 ◽  
Vol 8 (1) ◽  
pp. 8-19
Author(s):  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
E. I. Surikova ◽  
A. I. Shikhlyarova ◽  
I. V. Kaplieva ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Caspase 9 ◽  
Neurogenic Pain ◽  
Skin Cells ◽  
Similar Tendency ◽  
Thermo Fisher Scientific ◽  
Fisher Scientific ◽  
Melanoma Growth

Purpose of the study. Studying the dynamics of factors of apoptosis in mitochondria of skin and tumors cells in female mice with melanoma growth stimulated by chronic neurogenic pain. Material and methods. The study included female С57ВL/6 mice (n=56) with a model of chronic neurogenic pain (CNP) produced by the bilateral sciatic nerve ligation and with transplanted B16/F10 melanoma. After 1–3 weeks of the tumor growth, levels of cytochrome C, caspase‑9 (Bioscience, Austria), Bcl‑2 (Thermo Fisher Scientific, Austria), and AIF (RayBiotech, USA) were determined by ELISA, and levels of calcium (Са2+) were determined by the Arsenazo III method (Abris+, Russia) in mitochondria of tumors cells and skin not affected by the tumor growth. Results. In the CNP state, mitochondria of the skin cells showed a significant increase in Са2+ by 96.7 times, AIF by 1.4 times and Bcl‑2 by 5.9 times, while caspase‑9 decreased by 2.6 times, compared to the levels in intact mice. In the CNP‑stimulated melanoma growth, mitochondria of cells of the skin not affected by the tumor growth demonstrated a decrease in all studied indices, except caspase‑9 – its levels increased by 4.6 times after 3 weeks of the tumor growth. In mitochondria of the tumor cells within 1–3 weeks, levels of Са2+ decreased over time by 37.2–96.1 times, respectively, AIF by 49.4–2.0 times, Bcl‑2 by 3.0–1.5 times, cytochrome C by 15.3–8.8 times, and caspase‑9 increased by 1.7–4.4 times compared with the level in animals with pain. Conclusions. In general, the growth of melanoma stimulated by chronic pain and the standard melanoma growth were characterized by the opposite dynamics of levels of apoptosis factor both in mitochondria of skin cells and in mitochondria of tumor cells, with the exception of cytochrome C. Mitochondria of melanoma cells and of the unchanged skin have a similar tendency to change the levels of apoptosis factors, which may indicate their functioning in the conditions of the mitochondrial network at the level of one organ. Mitochondria of tumor cells provide the anti‑apoptotic state of the tumor itself and of the skin not affected by the malignant process, probably due to the stress state of the skin.

Comorbidity: Chronic neurogenic pain affects malignant growth and changes balance of neurosteroids in brain of rats.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Yulia A. Pogorelova ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Irina V. Kaplieva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Subclavian Vein ◽  
Tumor Development ◽  
Stress Factors ◽  
Male Rats ◽  
Control Group ◽  
Malignant Growth ◽  
Neurogenic Pain ◽  
Pulmonary Tissue ◽  
The Brain

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.

DYNAMICS OF CONCENTRATIONS OF NO-SYSTEM COMPONENTS DURING B16/F10 MELANOMA GROWTH IN FEMALE MICE WITH CHRONIC NEUROGENIC PAIN

2019 ◽  
Vol 65 (6) ◽  
pp. 898-903
Author(s):  
Oleg Kit ◽  
Yelena Frantsiyants ◽  
Inga Kotieva ◽  
Yekaterina Surikova ◽  
Irina Kaplieva ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Tumor Growth ◽  
Metabolic Regulation ◽  
Tumor Antigens ◽  
Immunological Tolerance ◽  
Neurogenic Pain ◽  
Female Mice ◽  
Tumor Tissues ◽  
Group 2 ◽  
Skin Conditions

Since chronic neurogenic pain has been reported to affect biological characteristics of B16/F10 melanoma, the purpose of the study was to analyze concentrations of components of the NO-system in mice during the growth of transplantable B16/F10 melanoma combined with chronic neurogenic pain. Methods. The study included 64 female mice. Melanoma was transplanted under the skin of the back to animals of the main group 2 weeks after the bilateral sciatic nerve ligation. Levels of NOS-3, NOS-2, endothelin-1, L-arginine, citrulline, total nitrite and ADMA were determined by ELISA in the intact skin and in tumor tissues. Results. The study showed that the dynamics of the studied parameters differed in tumor growth alone and in combination with chronic pain. Stably increased levels of NO-synthases in the tumor and stably increased ADMA levels with their decrease by week 3 of the growth were registered in the tumor growth with pain. Conclusions. Chronic pain probably contributes to the development of immunological tolerance to tumor antigens in the skin. Conditions are formed that facilitate the survival of tumor cells and contribute to the further development of melanoma. The dynamics of the NO-system activity can stimulate neoangiogenesis and enhance tumor invasion. Changes in the ADMA inhibitor levels in the tumor growth combined with chronic pain may indicate the control of NO levels through the metabolic regulation of NO-synthase activity, thus providing increased melanoma invasiveness.

Neurotrophins in the brain of C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with B16/F10 melanoma growing with comorbid pathology.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21557-e21557
Author(s):  
Elena M. Frantsiyants ◽  
Irina V. Kaplieva ◽  
Valeria A. Bandovkina ◽  
Ekaterina I. Surikova ◽  
Irina V. Neskubina ◽  
...  
Keyword(s):  
White Matter ◽  
Tumor Growth ◽  
Tumor Volume ◽  
Gene Knockout ◽  
Chronic Neuropathic Pain ◽  
Inhibition Of Tumor Growth ◽  
Growth Changes ◽  
The Brain ◽  
Melanoma Growth ◽  
Stimulation Of

e21557 Background: 10% of cancer patients have comorbidities accompanied by chronic pain. Neurotrophins and fibrinolytic system are involved in carcinogenesis and pain pathogenesis. The purpose of the study was to measure levels of neurotrophins in white matter of the brain of urokinase-deficient (uPA–) mice with B16/F10 melanoma growing in presence of chronic neuropathic pain (CNP). Methods: The study included female mice С57ВL/6 (normal genome uPA+, n = 40) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu (urokinase gene-knockout uPA–, n = 28) with B16/F10 melanoma (M) implanted subcutaneously 2 weeks after bilateral sciatic nerve ligation (CNP model). Intact mice (I) were controls. Levels of brain-derived neurotrophic factor BDNF, nerve growth factor NGF-β and neurotrophins 3 and 4 (NT3, NT4) were measured by ELISA in white matter of the brain after 3 weeks of tumor growth in presence of CNP. Results: Tumor volume in (uPA–) females by week 3 of carcinogenesis was 0.04 cm3, which was 70 times smaller than in (uPA+) females. Tumor volume in (uPA–) females with CNP was 5.76 cm3, which was 144 times larger than in (uPA–) females without CNP, and in (uPA+) females – 2.5 cm3. The brain of I (uPA–) showed higher levels of NT3 (by 1.3 times, p < 0.05), NT4 (by 2.6 times) and NGF-β (by 1.9 times, p < 0.05) and lower BDNF (by 1.7 times, p < 0.05), compared to I (uPA+). Both strains of mice with M or CNP demonstrated decreased levels of NGF-β, more pronounced in animals with a combination of these factors. (uPA–) females with CNP+M showed a decrease of NT3 and BDNF by 2 times, with NGF-β 2.2 times higher than in (uPA+) mice. Conclusions: The study revealed underlying differences in levels of neurotrophins in the brain of (uPA–) females which could contribute to the creation of conditions for the inhibition of tumor growth. Changes in the levels of NGF-β in mice with melanoma or CNP were nonspecific. Changes in the BDNF, NT3 and NGF-β balance in the brain of (uPA–) mice may be part of the mechanism of greater stimulation of melanoma growth under the influence of CNP.

Comorbidity affects Вcl-2 levels in mitochondria in C57BL/6 mice with transplantable B16/F10 melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21581-e21581
Author(s):  
Irina V. Neskubina ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Natalia D. Cheryarina ◽  
Alla I. Shikhlyarova ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Development ◽  
Brain Mitochondria ◽  
The Body ◽  
Heart Mitochondria ◽  
Control Group ◽  
Neurogenic Pain ◽  
Intact Group ◽  
Vital Functions ◽  
Thermo Fisher Scientific

e21581 Background: Overexpression of the Bcl-2 protein inhibits apoptosis and promotes carcinogenesis. Stress causes signaling leading to cell buffering with Bcl-2 protein above acceptable levels. The purpose of the study was to analyze the influence of comorbidity – chronic neurogenic pain (CNP) – on the Bcl-2 levels in mitochondria of cells of melanoma, the heart, skin and brain in female mice with growing tumors. Methods: Female С57ВL/6 mice were divided into groups: intact group (n = 21); control group with a CNP model – bilateral sciatic nerve ligation (n = 21); group M – B16/F10 melanoma (n = 63); CNP+M group – B16/F10 melanoma was transplanted 3 weeks after the CNP model creation (n = 63). The concentration of Bcl-2 (ng/mg of protein) was determined in mitochondrial samples by ELISA (Thermo Fisher Scientific, Austria). Statictical analysis of results: Statistica 10.0. Results: CNP decreased the Bcl-2 level in heart mitochondria by 1.3 times (p < 0.05), but increased it in skin and brain mitochondria by 5.8 and 1.3 times, respectively. Similar changes were observed in melanoma growth 1 week after its transplantation: Bcl-2 levels decreased in heart mitochondria by 1.3 times, and increased in the skin and brain by 8.9 and 1.3 times, respectively. After 2 weeks of the tumor growth, Bcl-2 in brain mitochondria decreased by 1.7 times, and it started declining in the skin by the 3rd week – by 4 times, compared to intact females. Bcl-2 in tumor mitochondria exceeded the values in the skin by more than 4 times throughout the experiment. Tumor growth in presence of CNP caused a decrease in Bcl-2 in brain mitochondria by 2.4 times after 3 weeks, and in the heart and skin – by 2 and 1.7 times, respectively, after 2 weeks. Bcl-2 in tumor mitochondria in presence of CNP was lower than in the intact skin on average by 1.8 times throughout the experiment. Conclusions: CNP as a comorbidity caused a modulating effect on the mechanisms of survival and apoptosis of cells both in the tumor and in the main organs providing the vital functions of the body - the brain and heart, and also affects the target organ of melanoma - the skin. The results demonstrated the ability of comorbidity to change levels of Bcl-2 in mitochondria depending on the stage of tumor development.

Apoptosis indices in liver cell mitochondria in B16/F10 melanoma growing in presence of chronic neurogenic pain

2021 ◽  
pp. 71-79
Author(s):  
Е.М. Франциянц ◽  
И.В. Нескубина ◽  
Е.И. Сурикова ◽  
А.И. Шихлярова ◽  
В.А. Бандовкина ◽  
...  
Keyword(s):  
Cytochrome C ◽  
G Protein ◽  
Tumor Development ◽  
Mitochondrial Fraction ◽  
Liver Mitochondria ◽  
Caspase 9 ◽  
Neurogenic Pain ◽  
Intact Group ◽  
Subcutaneous Transplantation ◽  
Melanoma Growth

Введение. Печень по количеству, плотности митохондрий один из самых богатых органов, который также является критическим местом для множества метаболических путей. Цель исследования - изучение показателей апоптоза в митохондриях печени самок мышей линии С57ВL/6 при самостоятельном росте меланомы В16/F10 и на фоне коморбидной патологии - хронической нейрогенной боли. Методика. В эксперименте использовали мышей-самок (n=168) линии С57ВL/6. Группы: интактная (n=21); контрольная (n=21) - создание модели хронической нейрогенной боли (ХНБ), путем двусторонней перевязки седалищных нервов; группа сравнения (n=63) - подкожная трансплантация меланомы B16/F10; основная группа (ХНБ+B16/F10) (n=63) - подкожная трансплантация меланомы В16/F10 через 3 нед после моделировия ХНБ. В митохондриях печени методом ИФА определяли концентрацию: цитохрома С (нг/г белка), каспазы 9 (нг/г белка), Bcl-2 (нг/г белка), AIF (нг/г белка), кальция (Са 2+) (мМоль/г белка). Результаты. В митохондриях клеток печени через 1 нед роста меланомы относительно интактных значений фиксировали нарастание уровней AIF в 2,2 раза, цитохрома С в 1,7 раза (р<0,05) и снижение каспазы 9 в 2,0 раза; через 3 нед - падение кальция в 4,7 раза, AIF в 7,1 раза и цитохрома С в 1,7 раза (р<0,05) и накопление каспазы 9 - 1,6 раза (р<0,05). Развитие опухоли при ХНБ через 1 нед сопровождалось уменьшением концентрации AIF в 29,3 раза и цитохрома С в 2,0 раза по сравнению с контрольными значениями (ХНБ). Через 3 недели роста меланомы на фоне ХНБ фиксировали снижение уровней AIF в 6,6 раза, цитохрома С в 4,7 раза и кальция в 32,8 раза, уровень каспазы 9, напротив, повышался в 1,5 раза (р<0,05). Заключение. Наличие коморбидной патологии - ХНБ при опухолевом процессе способствует раннему возникновению нарушений в электронно-транспортной цепи митохондрий клеток печени. Background. The liver is one of the richest organs in terms of the number and density of mitochondria; it is also a critical site for many metabolic pathways. The aim of the study was to analyze indicators of apoptosis in liver mitochondria in female С57ВL/6 mice with B16/F10 melanoma growing alone and in presence of chronic neurogenic pain. Methods. Female С57ВL/6 mice (n=168) were studied. Animals were divided into groups: intact group (n=21); controls (n=21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation; comparison group (n=63) with subcutaneous transplantation of B16/F10 melanoma; main group (CNP+B16/F10) (n=63) with subcutaneous transplantation of B16/F10 melanoma 3 wks after modeling CNP. Cytochrome C (ng/g protein), caspase-9 (ng/g protein), Bcl-2 (ng/g protein), AIF (ng/g protein), and calcium (Ca2+) (mmol/g protein) were measured by ELISA in the liver mitochondrial fraction. Results. After 1 wk of melanoma growth, AIF increased by 2.2 times, cytochrome C increased by 1.7 times (p<0.05), and caspase-9 decreased by 2.0 times compared to the intact group values. After 3 wks, calcium decreased by 4.7 times, AIF by 7.1 times, cytochrome C by 1.7 times (p<0.05), and caspase-9 increased by 1.6 times (p<0.05). After 1 wk, tumor development in the presence of CNP was accompanied by decreases in AIF by 29.3 times and cytochrome C by 2.0 times, compared to control CNP values. After 3 wks of melanoma growth in presence of CNP, AIF decreased by 6.6 times, cytochrome C by 4.7 times, and calcium by 32.8 times. Caspase-9, on the contrary, increased by 1.5 times (p<0.05). Conclusions. The presence of CNP comorbidity during the tumor development facilitates earlier occurrence of disorders in the electron transport chain of hepatocyte mitochondria.

INFLUENCE OF CHRONIC NEUROGENIC PAIN ON BRAIN NEUROTRANSMITTER SYSTEMS OF MALE MICE IN DYNAMICS OF MELANOMA GROWTH

2019 ◽  
Vol 65 (6) ◽  
pp. 920-924
Author(s):  
Oleg Kit ◽  
Yelena Frantsiyants ◽  
Valeriya Bandovkina ◽  
Irina Kaplieva ◽  
Inga Kotieva ◽  
...  
Keyword(s):  
Brain Cortex ◽  
Comparison Group ◽  
Main Group ◽  
Malignant Growth ◽  
Neurogenic Pain ◽  
Brain Neurotransmitter ◽  
Group 2 ◽  
The Brain ◽  
Neurotransmitter Balance ◽  
Melanoma Growth

Biogenic amines (BA) are known to be involved in the malignant growth, and their levels change in the CNS when exposed to pain; however, the combined effect of chronic pain and cancer on the BA dynamics in the brain has not been studied. The aim of the study was to evaluate characteristics of BA balance in the brain cortex during melanoma growth with chronic neurogenic pain (CNP). Material and methods. The study included 64 male C57Bl/6 mice weighing 22-24 g. В16/F10 melanoma was transplanted under the skin of the back to animals of the main group 2 weeks after the sciatic nerve ligation. Mice with melanoma without pain were the comparison group. Levels of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine, and 5-HIAA were determined by ELISA. Results. Changes in adrenaline levels were registered in the brain of mice with CNP. The growth of melanoma in males was accompanied by elevated brain levels of adrenaline and noradrenaline and decreased dopamine and serotonin. Similarities in the direction of shifts in the neurotransmitter profile were observed in melanoma development with and without CNP. Conclusions. The influence of CNP on the neurotransmitter balance in the CNS was probably one of the factors that influenced the course of transplanted B16/F10 melanoma in males of the main group.

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