S. V. Michurina

Hepatocyte Apoptosis in Rats Exposed to Benzo(a)pyrene

We studied the effect of benzo(a)pyrene on activity of nuclear endonucleases and expression of molecular regulator of apoptosis Bcl-2 in liver cells in rats. Intraperitoneal injection of benzo(a)pyrene (in a total dose of 60 mg/kg body weight) reduced activity of nuclear endonucleases in the liver cells, which attests to inhibition of apoptosis by the nuclear pathway. Injection of the toxicant enhanced the expression of intracellular molecular regulator of apoptosis Bcl-2 protein in the liver cells, which attested to triggering of proapoptotic signaling in these cells and organism’s attempts to limit the development of apoptosis by the mitochondrial mechanism via activation of Bcl-2-dependent anti-apoptotic defense.

Changes in the Structure of the Thymus under Conditions of Various Treatments for Experimental Mammary Tumor

Morphological changes in the thymus of female Wistar rats with experimental mammary gland carcinomas were studied. After adjuvant therapy, the area of the cortical matter and density of parenchymal cells in the thymus decreased, while areas of the medulla, connective tissue, and content of immunoblasts and macrophages increased. In the thymuses of rats receiving exogenous DNA, morphological signs of activation of the lymphoid and epithelial components were found: areas of the cortex and medulla, glandular and connective tissue corresponded to the values in intact animals, the counts of lymphocytes in the central part of the cortical matter and of macrophages in all zones of the thymus increased, and lymphocyte migration from the thymus increased (in comparison with the chemotherapy group).

The Thymus in Experimental Mammary Carcinogenesis and Polychemotherapy

Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus. Animals of the experimental tumor+chemotherapy group exhibited morphological signs of lymphocyte migration from the thymus and suppressed activities of the lymphoid and epithelial components (lesser area of connective tissue elements and glandular tissue, lesser density of parenchymatous cell elements, lesser counts of immunoblasts and small lymphocytes, and larger area of the medulla) in comparison with animals without chemotherapy.

Effect of Natural and 24-h Illumination on Mesenchymal Stem Cells

We studied the effect 24-h illumination on quantitative and qualitative parameters of the bone marrow cells in Wistar rats. It was shown that desynchronosis reduced the release of nucleated cells from the femoral bone, while melatonin weakened this effect. The number of bone marrow mesenchymal stromal cells was resistant to circadian rhythm disturbances, while proliferation depended on glucose concentration in the medium.

Regional Lymph Nodes in the Liver of Rats in Functional Pinealectomy

The effects of functional pinealectomy on the morphological organization of the regional lymph nodes in the liver of rats were studied. Shrinkage of follicles (with increased percentage of germinative centers in them) and reduced count of mature lymphoid cells in the medullary cords indicated more intense migration of B cells from these B-dependent zones. High counts of medium and small lymphocytes in the paracortical zone reflected increasing release of circulating T cells from the blood. Intensification of pinocytosis in dendritic (interdegitating) cells and of fibroblastic reticular cells and activation of protein synthesis in plasma cells indicated activation of immune reactions. Increase in the relative area of lymph node sinuses reflected strained status of their drainage system.

Effect of Experimental Desynchronosis on Immunotoxicity of Benz(a)pyrene in (CBA×C57Bl)F1 Mice

Experiments on (CBA×C57Bl)F1 mice showed that constant (day and night) illumination for 2 weeks led to the development of internal desynchronosis, which significantly modulated the reaction of the immune system to benz(a)pyrene compared to those in intact animals. Presumably, the differences were associated with changed circadian rhythms of the immune parameters in experimental animals determining different ratios and, presumably, functions of immunocompetent cells during benz(a)pyrene exposure in intact controls and animals with desynchronosis.

Effect of Various Treatment Modes of Experimental Mammary Gland Tumor on Structure of Anterior Mediastinal Lymph Nodes

The effects of various treatment modes on the morphology of anterior mediastinal lymph nodes were examined in female Wistar rats with chemically provoked breast cancer. Adjuvant chemotherapy impaired filtration barrier potential of the anterior mediastinal lymph nodes, which manifested in increased volume of sinuses, reduced volumes of lymphoid nodules with germinal centers and thymus-dependent regions, down-regulated proliferative activity of lymphoid cells in B-cell zone and paracortex, and diminished macrophage score in all zones. Intraperitoneal injection of double-stranded DNA preparation (5 mg/kg) activated the humoral and cellular immune responses manifested by morphological alterations in anterior mediastinal lymph nodes observed in parallel with a decrease of medullary sinuses volume: enhancement of lymphocyte volume and lymphocyte score in paracortex, mantle zone expansion, and an increase of volume of the light centers in lymphoid nodules paralleled with diminished proliferative activity in them.

Anterior Mediastinal Lymph Nodes in Chemically Induced Breast Cancer

The anterior mediastinal lymph nodes were analyzed morphometrically in rats with chemically provoked breast cancer. Rats with untreated breast cancer and animals receiving chemotherapy demonstrated decreased volumes of paracortical region and lymphoid nodules with the germinal centers accompanied by extended medullary thymic substance. Resection of largest focus of breast tumor improved the filtration barrier potential of anterior mediastinal lymph nodes, up-regulated the proliferative activity of lymphoid cells in T-cell zones, and down-regulated proliferation of plasmatic cells.

Changes in Peripheral Blood Monocytes and Liver Macrophages in Male Rats after Benzo(a)pyrene Injection

Intraperitoneal injections of benzo(a)pyrene to male rats in a total dose of 60 mg/kg modified the production of ROS and the phagocytic potential of blood monocytes by modulating their potential bactericidal activity. The lysosomal system (particularly the secondary lysosomes) of liver macrophages was activated, which promoted fusion of the hydrolytic potentials of macrophages and monocytes. These results indicated that the toxin modulated the cellular immune homeostasis and the level of general nonspecific resistance.

Effect of Melatonin on Cellular Composition of the Spleen and Parameters of Lipid Metabolism in Rats with Alimentary Obesity

We studied the effects of melatonin on the status of immune organs and parameters of lipid metabolism in rats with alimentary obesity and parameters of lipid metabolism and immune status in Wistar rats kept on high-fat diet and receiving melatonin solution per os. Melatonin leveled the changes in blood and liver parameters of lipid metabolism, which was paralleled by normalization of cellular composition of immune organs. We conclude that melatonin can be a promising agent for the treatment of lipid metabolism and immune status disorders in alimentary obesity.