Effect of animal venom toxins on the main links of the homeostasis of mammals (Review).

The human body is affected by environmental factors. The dynamic balance between the organism and its environment results from the influence of natural, anthropogenic and social aspects. The factors of exogenous origin determine development of adaptive changes. The present article summarises the mechanisms of animal venom toxins and homeostasis disruption in the body of mammals. The mechanisms underlying pathological changes are associated with shifts in biochemical reactions. Components of the immune, nervous and endocrine systems are key in the host defense and adaptation processes in response to venom by triggering signalling pathways (PI3kinase pathway, arachidonic acid cascade). Animal venom toxins initiate the development of inflammatory processes, the synthesis of pro-inflammatory mediators (cytokines), ROS, proteolytic enzymes, activate the migration of leukocytes and macrophages. Keratinocytes and endothelial cells act as protective barriers under the action of animal venom toxins on the body of mammals. In addition, the formation of pores in cell membranes, structural changes in cell ion channels are characteristic of the action of animal venom toxins.

EFFECT OF SCORPION VENOM TOXINS ON STRUCTURAL AND FUNCTIONAL PARAMETERS OF INTERNAL ORGANS, INCLUDING KIDNEYS (REVIEW).

OBJECTIVE: The aim: To establish patterns of structural and functional changes in internal organs, including kidneys, under the conditions of exposure to scorpion venom toxins. PATIENTS AND METHODS: Materials and methods: A thorough literature analysis was conducted on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. When processing the search results, we chose the newest publications up to 5 years old or the most thorough publications that vividly described the essence of our topic. CONCLUSION: Conclusions: The venom of various species of scorpions exhibits a wide range of biological activity. Acting on the structures of the central and peripheral nervous system, the toxins of scorpion venom cause the development of paralysis, convulsions, brain inflammation, hemorrhagic and ischemic strokes. Under conditions of influence on the cardiovascular system, damage to the endothelial lining of the vascular wall, disturbances in heart rhythm, conduction, and the development of destructive changes in the myocardium are characteristic. Data on kidney damage due to scorpion bites require a more detailed study, as information on microscopic and submicroscopic changes in the structure of the organ is too limited. However, cases of the development of tubular necrosis, interstitial nephritis, and kidney infarction are currently known.

Plasma Levels of MMPs and TIMP-1 in Patients with Osteoarthritis After Recovery from COVID-19.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. OBJECTIVE: In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. METHODS: The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. CONCLUSION: Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

INTERDEPENDENCE OF THE MICROBIOCENOSE COMPOSITION OF BIOPELLICLE AND THE SEVERITY DEGREE OF CHANGES IN THE MUCOSA OF THE GUMS AFTER TEN WEEKS OF EXPERIMENTAL OPIOID EXPOSURE.

OBJECTIVE: The aim: To study the relationship between the degree severity of changes in the tunica mucosa of the rats gums and the composition of the microbiota of tooth surface in the gingival margin under the ten-week action of the opioid. PATIENTS AND METHODS: Materials and methods: The study was performed on 34 male rats, weighing 160 - 255 g, aged 4.5 - 7 months. Animals were administered nalbuphine for 10 weeks, gradually increasing the dose (0.212 - 0.283 mg/kg). The research of the bacterial from the microbiotope of tooth surface in the gingival margin of rats was performed using statistical analysis of quantitative results. RESULTS: Results: The 4 stages of development of the pathological process and changes in the qualitative and quantitative composition of the microbiocenosis in the gingival margin of the oral mucosa are determined. Depending on the severity of pathological changes in the mucous membrane of the gums of rats under the long-term action of the opioid, a significant increase in the quantitative indicators of bacterial species of pathogenic and opportunistic microbiota at degree IV of the process compared with degree I. The appearance of potential pathogens of purulent-inflammatory processes - Klebsiella and Pseudomonas aeruginosa was noted. CONCLUSION: Conclusions: The relationship between the quantitative and qualitative characteristics of the microbiocenosis of tooth surface in the gingival margin and the severity of changes in the mucous membrane of the of rats gums under the ten-week action of the opioid was determined, indicating bacterial associations of dental biopellicle as an etiological factor.

INFLUENCE OF COMBINED PHARMACOTHERAPY ON CARDIO-VASCULAR SYSTEM OF ARTERIAL HYPERTENSION (IN EXPERIMENT).

OBJECTIVE: The aim: Study of the patterns of structural changes in the left ventricular myocardial capillaries of rats with arterial hypertension with combined pharmacotherapy with Bisoprolol and Thiotriazolinum. PATIENTS AND METHODS: Materials and methods: Experiments were conducted on 30 line rats with congenital stress-induced arterial hypertension: 10 animals without treatment and 10 animals with treatment. Pharmacological correction of spontaneous arterial hypertension was performed with 20 mg / kg of Bisoprolol and 50 mg / kg of Thiotriazolinum per os once a day. Pharmacotherapy began at 5 months of age, that is, at a time when compensated heart failure was formed in rats with arterial hypertension. Animals were withdrawn from the experiment 100 days after the start of the correction. Control was provided by intact animals (10 rats) of the corresponding age. While extracted from the experiment rats of all experimental groups had their arterial pressure measured using a plethysmograph, electron microscopic examination of the left ventricular myocardium and morphometric study of volumetric and quantitative densities, cross-section area and form factor of micropinocytotic vesicles were conducted. RESULTS: Results: In rats with arterial hypertension after application of Bisoprolol and Thiotriazolinum, arterial pressure significantly decreases in experimental rats compared to animals without correction. The number of capillaries in the myocardium after pharmacotherapy increases up to control values, which shows their reparation. In most endothelial cells, organelles retain their integrity and presence that are characteristic of intact rats. The well-expressed processes of transcytosis are shown by the statistical similarity of the quantitative density and the size of the micropinocytotic vesicles in the endothelial cells of the myocardium capillaries of compared experimental animals. CONCLUSION: Conclusions: In rats with arterial hypertension, the combination of Bisoprolol and Thiotriazolinum prevents the decrease in the number of capillaries in the myocardium of the left ventricle, promotes the preservation of the ultrastructure of their endothelial cells and maintains the processes of transedothelial transfer of substances at the level of intact animals.

Morphofunctional status of cardio-vascular system of rats with arterial hypertension.

OBJECTIVE: The aim: Was to clarify the general patterns of structural changes in the left ventricular myocardial capillaries in rats with spontaneous arterial hypertension. PATIENTS AND METHODS: Materials and methods: Experiments were conducted on 50 ISIAH (inherited stress-induced arterial hypertension) line rats with arterial hypertension: juvenile young (45-day) and sexually mature (100-day) rats, as well as intact animals of the corresponding age. While extracted from the experiment rats of all experimental groups had their arterial pressure measured using a plethysmograph. Electron microscopic examination of the left ventricular myocardium and morphometric study of volumetric and quantitative densities, cross-section area, and form factor of micropinocytotic vesicles were conducted. RESULTS: Results: In sexually mature rats with arterial hypertension, a high level of pressure is maintained. In 45-day-old rats with arterial hypertension in endothelial cells of myocardial blood capillaries there is a hyperactivation of biosynthetic processes (euchromatic nucleus, large-sized mitochondria, ER canals, Golgi complex), which may be a manifestation of reactive processes in response to a non-stable increase in arterial pressure. In the 100-day rats with arterial hypertension, the mosaic of the ultrastructure of the myocardium blood vessels is preserved, but destructively-dystrophic changes become more expressive and involve not only the organelles but also the integrity of the endothelial cell itself. Destructively-dystrophic processes in rat capillaries are accompanied by compensatory and adaptive ones. This is manifested by activation of the transport of substances, both transendothelial and paracellular, and quantitative density of micropinocytotic vesicles increases statistically significantly. CONCLUSION: Conclusions: In myocardial capillaries of young (45-day) arterial hypertension rats, compensatory and adaptive changes are manifested by activation of biosynthetic processes in endothelial cells following a slight increase in micropinocytotic vesicles quantitative density and signs of destructive-dystrophic processes (minor edema and lysis of endothelial cell cytoplasm). In sexually mature (100-day) arterial hypertension rats in the blood capillaries of the myocardium, the destructive-degenerative changes increase is accompanied by preservation of signs of compensatory processes. Reducing the number of capillaries is offset by an increase in the number of micropinocytotic vesicles.

The influence of drug treatment on cardio-vascular system of the rats with congenital hypothyroidism.

OBJECTIVE: Introduction: In the treatment of hypothyroidism substitution therapy with L-thyroxine is used, it is also advisable to use the metabolites with membrane-stabilizing properties that normalize the metabolism in the body, for example, calcitonin, which significantly reduces the depth of the dystrophic phenomena in the myocardium. The aim was to study the patterns of structural changes in the left ventricular myocardial capillaries of rats with congenital hypothyroidism in combinative drug therapy with L-thyroxine and calcitonin. PATIENTS AND METHODS: Materials and methods: 30 white Wistar line rats were used as experimental animals: 10 with treatment and 10 without as well as control - 10 intact Wistar line rats of the same age. Mercazolil was used to inhibit thyroid gland in order to model congenital hypothyroidism. After birth, the rats received L-thyroxine at a dose of 10 µg / kg per os daily, calcitonin at a dose of 1.0 MU / kg per day intramuscularly, then with mother's milk, later by themselves for 100 days. The arterial pressure was measured in all experimental groups during extraction from the experiment by plethysmograph, their left ventricular myocardium was examined under electron microscope and micropinocytotic vesicles in their cells were studied morphometrically. RESULTS: Results: In rats with congenital hypothyroidism, for which L-thyroxin drug in combination with calcitonin was used as a substitution therapy, after pharmacological correction, in general there is no pronounced heteromorphism of the ultrastructure of the left ventricular myocardial blood capillaries, which was characteristic for animals without pharmacological correction. The analysis showed normalization of the content of free thyroxine in blood plasma and blood pressure of rats with congenital hypothyroidism after complex substitution therapy. CONCLUSION: Conclusions: In rats with congenital hypothyroidism, which received L-thyroxine and calcitonin at birth, the myocardium capillaries generally remain intact and have morphological and functional characteristics similar to intact animals, which is the theoretical basis for the need for calcitonin to be used in substitution therapy in hypothyroidism.