NANOPARTICLES AND COLORECTAL CANCER: CAN THE USE OF METAL NANOPARTICLE COMPOSITIONS AFFECT OXIDATIVE STRESS MARKERS AND COLON HISTOLOGICAL CHANGES UNDER DMH-INDUCED CARCINOGENESIS.

Colorectal cancer (CRC) - a significant global health challenge. Exploring biological markers of oxidative stress is crucial, as they can play an essential role in initiating the transition from an organ's "healthy state" to a "malignant injury." There is substantial promise in investigating the level of 8-isoprostane (8-isoPGF2α) as a novel and dependable marker of oxidative stress. This paper presents that 8-isoprostane levels have been linked to the development of severe structural changes in the colon wall, accompanied by endogenic intoxication syndrome. The obtained results prove the strong connection between oxidative stress and carcinogenesis progression. Our research further illustrates the favorable and potentially beneficial impact of the Au/Ag/Fe NPs composition, which can find utility in a diverse range of contemporary applications.

[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.

[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.

[VIOLATION OF THE PROOXIDANT-ANTIOXIDANT BALANCE IN THE SPLEEN TISSUE UNDER EXPERIMENTAL CARCINOGENESIS].

This study was devoted to the investigation of antioxidant homeostasis in spleen tissue of white rats in the dynamics of development of colon adenocarcinoma induced by the introduction of sym-dimethylhydrazine (DMH). The effectiveness of the antioxidant barrier (Cu,Zn-superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione) and oxidative damage products (TBARS, advanced oxidation protein products, diene and triene conjugates, Schiff bases) were measured in the homogenate of spleen tissue. A violation of the redox balance due to the accumulation of lipid peroxidation products, a decrease in the activity of antioxidant enzymes and antioxidant mediators of non-enzymatic nature was established. The development of oxidative stress leads to disruption of the synthesis of glutathione peroxidase and glutathione reductase in the endoplasmic reticulum, i.e., to inhibition of the functional activity of the glutathione-dependent unit of the antioxidant system. DMH-induced carcinogenesis is associated with enzymatic/non-enzymatic redox imbalance as well as increased oxidative damage to proteins and lipids. Evaluation of redox biomarkers can be potential diagnostic indicator of colon adenocarcinoma advancement.

CHANGES OF CYTOLYSIS INDICATORS IN RATS' BLOOD RESULTED FROM SIMULTANEOUS INTOXICATION WITH TOBACCO SMOKE AND SODIUM NITRITE AFTER USING MILDRONATE.

The article is devoted to an experimental study of the effect of tobacco smoke and the effect of sodium nitrite on the background of tobacco intoxication on the body of rats of different age groups and to identify violations caused by these toxicants. It has been established that under the conditions of nitrite-tobacco intoxication, a more pronounced cytolysis of the cells takes place, which leads to a change in the permeability of the plasma membranes than in case of poisoning with only tobacco smoke. Immature rats were the most sensitive to the action of toxicants, in which the activity of membrane-dependent enzymes was more statistically significant (ALT activity in the serum increased 7,7 times, AST - 5 times, GGTP - 4,1 times, LDH - 1,8 times; p ≤ 0.05) at the end of the study. In the same group of rats, the highest percentage of permeability of the erythrocyte membrane was revealed, as indicated by its index (55,6% higher than normal, in mature animals 38% EII was higher than in intact control animals, in old ones - 54%). When using an antihypoxant, it was noted that mildronate significantly (p≤0.05) reduced the activity of indicator enzymes in the blood serum of rats during the whole experiment, and also led to a decrease in the erythrocyte index of intoxication in the blood of rats of all age groups. To confirm the obtained results, morphological studies of the organs of rats of different age groups were carried out after sodium was damaged by nitrite against the background of tobacco intoxication and the effect of the metabolic action of mildronate on them. The membrane-protective properties of mildronate have been proven, which makes it possible to use it in various pathologies accompanied by the development of cytolytic syndrome.

HISTOLOGICAL CHANGES IN SPLEEN UNDER CONDITIONS OF TOXIC CARCINOGENESIS.

Under development of dimethylhydrazine-induced adenocarcinomatosis of the large intestine in white outbred male rats morphological changes of the structural components of the spleen were studied. It was found, that the progression of experimental carcinogenesis is accompanied by severe violations of the morphological state of all structural components of the spleen, manifested by destructively degenerative changes of the stroma, red and white pulp and significant vascular disorders. The severity of the pathomorphological changes in the spleen increases directly proportionally to the increase of the duration of the oncogenic factor impact.

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.

SORPTION CORRECTION OF NEPHRON SUB-MICROSCOPIC CHANGES CAUSED BY NEOPLASTIC CHRONIC INTOXICATION WITH THE APPLICATION OF CYTOSTATIC THERAPY.

The electron microscopic changes of the nephron structural components under conditions of dimethylhydrazine (DMH)-induced carcinogenesis with the development of colorectal adenocarcinoma in situ were evaluated. Destructive changes in epitheliocytes of proximal and distal tubules of the nephron, microcirculation disturbances in renal corpuscles and tubular structure are evidences of disorder in urine formation stages. Аdministration of cytostatics aggravates the degree of destructive changes in the kidney. The application of carbon enterosorbent of IV generation "Carboline" for chronic neoplastic endotoxemia correction in combination with chemotherapy components significantly reduces the structural changes of the cortical substance of the kidneys, activates processes of reparative regeneration. The normalization of the morphological structure of the nephron components is an indication of the recovery of the test organ functions.