[MORPHOLOGICAL CHANGES IN THE LIVER OF MICE WITH ANTIPHOSPHOLIPID SYNDROME AND ADMINISTRATION OF NITRIC OXIDE SYNTHESIS MODULATORS].

The aim of the research is to study the effect of L-arginine, the precursor of nitric oxide, and aminoguanidine, the inhibitor of inducible nitric oxide synthase, on morpho-functional changes in the liver of BALB/c mice with antiphospholipid syndrome. The study was carried out on 50 female BALB/c mice modelled with antiphospholipid syndrome. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for its correction. The material for microscopic study was taken by the method of Horalsky. The liver tissue samples were stained with hematoxylin and eosin. Significant hemodynamic disorders with manifestations of thrombosis in the liver in cases of antiphospholipid syndrome followed by destructive-degenerative changes of the stoma and parenchyma have been established. Administration of L-arginine in antiphospholipid syndrome caused restoration of the lobular and beam organization of the liver. The maximum effect on the morphological state of the liver was observed in using a combination of L-arginine and aminoguanidine. The protective effect of L-arginine and aminoguanidine on the microcirculation has been proved that evidences liver function restoration in mice with antiphospholipid syndrome.

[NEUROPROTECTIVE EFFECT OF AMINOGUANIDINE IN EXPERIMENTAL OBSTETRIC ANTIPHOSPHOLIPID SYNDROME].

The aim of the research was to investigate the effect of aminoguanidine on the content of autoantibodies in the serum, nitric oxide synthesis (NO), glial fibrillary acidic protein (GFAP) content and indicators of free radical oxidation in the cerebral hemispheres of BALB/c mice with antiphospholipid syndrome (APS) on the 18th day of pregnancy. An increase in the content of autoantibodies to brain proteins (120 kDa, 150 kDa, and >170 kDa) was detected in the serum of BALB/c mice with APS on the 18th day of pregnancy. An increase in the content of GFAP (total), GFAP (49-37 kDa), NO2¯, NO3¯ and prooxidant-antioxidant system imbalance in the cerebral hemispheres of pregnant mice with APS was established. With administration of aminoguanidine into the pregnant mice with APS, a decrease in the content of autoantibodies to brain proteins (120 kDa and 150 kDa) in serum was proved. With the introduction of aminoguanidine, a selective inhibitor of inducible NO synthase on the 18th day of pregnancy the increase in GFAP (49-37 kDa) in the cerebral hemispheres of APS mice was established, and the GFAP (total), NO2¯ and NO3¯ content did not change significantly, relative to the indicators of pregnant animals with APS. With introduction of aminoguanidine in cases of APS on the 18th day of pregnancy lesser manifestations of oxidative stress in the cerebral hemispheres, a decrease in the activity of lipid peroxidation processes, an increase in the activity and content of the antioxidant system components was evidenced. Thus, aminoguanidine has a neuroprotective effect in obstetric antiphospholipid syndrome in the BALB/c mice.

[PRODUCTION OF REACTIVE OXYGEN SPECIES AND DEVELOPMENT OF APOPTOSIS IN BLOOD LEUKOCYTES IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME].

The aim of the study is to investigate the processes of apoptosis and the level of formation of reactive oxygen species (ROS) in blood cells of BALB/c female mice in experimental antiphospholipid syndrome (APS). The content of living, apoptotic and necrotic cells in blood leukocytes was evaluated. Apoptosis in cells was detected using Annexin V conjugated to GFP and propidium iodide. ROS in blood leukocytes were detected using 2',7'-dichlorofluorescein diacetate. The redistribution between the leukocytes populations was assessed by the magnitude of direct (FS) and lateral (SS) light scattering on the flow cytofluorimeter. It was established that the APS reduced the viability of blood leukocytes compare to the control. It is likely that their death is due partly to the activation of apoptosis. In the animals with APS a redistribution between the two main types of leukocytes (granulocytes and agranulocytes) was found out. An increase in the number of granulocytes in the blood was evidenced in cases of APS. It was established that the basal level of ROS production in granulocytes reduced by 27% and in agranulocytes - by 19% compare to the control. Thus, taking into account the attained results it can be argued that in the pathobiochemical mechanisms of APS development the enhanced activation of apoptosis and deficient formation of ROS is significant.

EFFECT OF TOBACCO SMOKE ON ROS PRODUCTION AND INFLAMMATION IN RATS OF DIFFERENT AGE.

The aim of our study was to investigate the effect of tobacco smoke on the content of reactive oxygen species (ROS) and level of cytokines in blood of rats of different age groups. For the purpose of carrying out the dosage, the beards of the white mongrel male rats were sub-divided into three groups: immature, mature and senile rats. Rat experimental groups were exposed to tobacco smoke daily for 45 days. The model of dependence on the chronic action of tobacco smoke was created using a sealed chamber in volume of 30 liters, which allowed to immerse animals in free behavior. Blood and blood serum was used for research. The isolation of neutrophils and lymphocytes from the blood was carried out by the method of gradient centrifugation on the double gradient of density ficol-verografin. The ROS production level was analyzed according to the intensity of the fluorescence. The immune enzyme method, using test systems in the blood serum, determined the level of proinflammatory cytokine, interleukin 6 (IL-6) and anti-inflammatory - interleukin 4 (IL-4). It was found that exposure to tobacco smoke in rats developed oxidative stress, as evidenced by increased formation of ROS in neutrophils and blood lymphocytes of all the study groups of animals. In this case, the level of ROS depends not only on the age of the animals, but also on the duration of the action of tobacco smoke. In the blood serum of all age groups of rats, pronounced changes in IL-6 content were observed on the 45th day of exposure to tobacco smoke. The highest IL-6 content was observed in immature rats at the end of the experiment. . At the same time, the content of anti-inflammatory cytokine IL-4 was significantly decreased in all age groups of animals. The results indicate an imbalance between the level of pro- and anti-inflammatory cytokines, in particular IL-6 and IL-4. The result of exposure to tobacco smoke is the development of oxidative stress and inflammatory processes that depend on the duration of the smoke, its concentration, the age of the animals, and other biologically active constituents.