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.

MICROSCOPIC CHANGES OF THE KIDNEY IN EXPERIMENTAL HYPERHOMOCYSTEINEMIA ON THE BACKGROUND OF HYPER- AND HYPOTHYROIDISM.

Hyper- and hypothyroidism are two typical clinical conditions that can cause a variety of metabolic changes, including impaired sulfur-containing amino acids metabolism, increased risk of cardiovascular disease, renal dysfunction, and renal failure. Hypothyroidism has been shown to be associated with increased serum creatinine, decreased glomerular filtration rate, and an increased risk of chronic kidney disease. At the same time, the pathophysiological mechanisms of renal dysfunction induced by excessive iodothyronine secretion are poorly understood. The aim of the study was to establish the reorganization of the kidney structural components under the conditions of experimental hyperhomocysteinemia (HHCy), hyper- and hypothyroidism and their combined effects. Thiolactone HHCy was simulated by administering to animals exogenous homocysteine ​​(HC) in the form of thiolactone at a dose of 100 mg/kg body weight once a day for 28 days. Hyperthyroidism was simulated by daily administration of L-thyroxine at a dose of 200 µg/kg on 21st day, hypothyroidism - daily administration of mercazolyl at a dose of 10 mg/kg on 21st day. Separate groups of animals were administered L-thyroxine and mercazolyl in parallel with HC. A significant degree of dystrophic changes in the structural components of the kidneys under conditions of simulated hyperthyroidism and HHCy was established. Signs of vascular insufficiency in the kidneys were detected. Deformation of renal corpuscles, single focal thickenings and destruction of the outer layer of the renal corpuscle capsule were observed, there was a narrowing of the urinary space in the capsule. Microscopic study of the kidneys of animals under the combined effects of hypothyroidism and HHCy revealed the most significant destructive-degenerative changes in the filtration and reabsorption apparatus of the organ on the background of significant vascular disorders. An increase in number of glomeruli and a decrease of the urinary space of the Shumlyansky-Bowman's capsule were observed in the renal corpuscles. Podocytes underwent significant destructive changes. Damage to the epithelium in the system of tubules was manifested by cell hypertrophy. Under the conditions of simulated HHCy, hyper- and hypothyroidism, and especially with their combined effect, there are significant disorders of the vascular bed with remodeling of the vascular wall. On the background of hemodynamic disorders, there are significant destructive and dystrophic changes in the epitheliocytes of the renal corpuscles of the Shumlyansky-Bowman's capsule, the proximal and distal tubules of the nephron, the filtration and reabsorption apparatus of the nephrons of the organ.

EFFECT OF XENOGRAFTS SATURATED WITH SILVERNANOCRYSTALS ON HISTOLOGICAL STRUCTURE OF THE SKIN IN THE DYNAMICS OF EXPERIMENTAL THERMAL INJURY.

The aim of this study was to establish histological state of the components of the affected area of skin in cases of application of xenograft saturated with silver nanocrystals in the dynamics after experimental thermal injury. The study was performed on 54 adult guinea pigs following the rules of bioethics. Experimental animals were divided into two groups: the 1st - animals with severe thermal injury (27); the 2nd - animals with burn injury (27), in which the wounds were covered with xenograft after early necrectomy of the damaged tissues. To investigate the microscopic changes in the skin the animals were removed from the experiment on the 7th, 14th, and 21st days of the experiment. Histological sections were stained with hematoxylin and eosin. Application of xenograft saturated with silver nanocrystals for 7 days contributes to formation of granulation tissue, activation of regenerative mechanisms in the marginal areas of the wound. On the 14th day of the experiment, an epidermal regenerate was evidenced at the wound, its formation source was the perifocal areas of the epidermis and skin appendages, and below it - fibroblastic cells rich granulation tissue, well-defined fibrous structures, equally set components of the hemomicrocirculatory flow. On the 21st day, a well-formed epidermis with a clear differentiation of cells into layers was observed. In the fresh connective tissue, formation of papillae with new capillaries embedded in the epithelium was evidenced. There were collagen as well as elastic fibres among the fibrous structures of the intercellular substance of the connective tissue. In all stages of the experiment with application of xenograft saturated with silver nanocrystals no purulonecrotic masses were observed in the affected area. Thus, histologically it has been found out that application of xenograft saturated with silver nanocrystals after early necrectoна руссmy of burn-damaged areas of the skin at an early stage improves formation of granulation tissue. In the late post-experimental thermal injuries, their usage accelerates epithelialization, connective tissue formation and has positive effect on the course of the experimental burn wound process.

[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.

[MICRO- AND ULTRASTRUCTURAL RECONSTRUCTION OF THE RAT SUBMANDIBULAR GLAND IN THE LATE STAGES OF EXPERIMENTAL TYPE 2 DIABETES MELLITUS].

Electron microscopic investigations of the animals' submandibular gland, conducted in 6 weeks of the experiment, established that ultrastructural changes increase in glandular cells of terminal secretory units in comparison with early period of the experiment. Serocytes have osmiophilic, rather small or picnotic nuclei. Perinuclear spaces of karyolemma are uneven, external nuclear membrane forms local protrusions. Electron density of the karyoplasm is significant, appearing homogenous, nuclei are not observed. Evident submicroscopic changes in blood capillaries of the submandibular gland in experimental diabetes mellitus indicate the impairment of blood-tissue barrier and transcapillary exchange. Deep destructive modifications of all branches of microcirculatory blood flow of the submandibular gland are observed in 8-week course of experimental diabetes mellitus. As compared with the 6th week of investigation, a reliable slight dilation of organ artery diameter, dilation of the diameter of interlobular arterioles, dilation of the diameter of intralobular (precapillary) arteriole and dilation of the capillary diameter were observed. Dilation, as compared to 6th weeks of the experiment, of postcapillary venules was observed. Compared to the indices of the 6th weeks of the experiment, an index of trophic activity of the submandibular gland tissuereaches its maximum meaning and an index of packing density of the capillaries reaches its minimum meaning. Capillary network loses delicate, tortuous pattern and often breaks due to destruction of the capillary component. Arteriovenous anastomoses dilate and blood from the arterioles flows into the venous bed avoiding destructed capillaries. Venules are dilated; thin-walled, retained fragments of the capillaries are significantly dilated in some areas. Swelling of connective tissue stroma and significant swelling of the interstitium are observed. Walls of the capillaries and venules are deformed. The walls of the arterioles are thickened due to plasmorrhagia, sclerosis and hyalinosis.

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.