Analysis of functional changes under using of candesartan cilexetil with resveratrol in animals

Cardiovascular diseases are widespread throughout the world. The incidence of diseases of the cardiovascular system has increased several times. Cardiovascular diseases have become the leading cause of death in many countries. Currently, the efforts of many researchers are aimed at studying and creating new, more effective and safe drugs and their combinations for the treatment of pathology of the cardiovascular system. Candesartan cilexetil is an angiotensin II receptor antagonist. It is used medicinally as a long-acting antihypertensive agent. However, this drug has a number of side effects. Resveratrol is a natural antioxidant. This substance exhibits pleiotropic effects, including antioxidant, anti-inflammatory, anti-aging, cardioprotective, and neuroprotective activities. The aim is investigation of acute toxicity of candesartan cilexetil and resveratrol in combination in vivo. Male and female ICR mice were used for the experiment. Animals received candesartan cilexetil and resveratrol intragastrically once. Evaluation of the effects of substances on internal organs (heart, spleen, kidneys, lungs, liver and brain) was carried out in 2 weeks after the introduction of the substances. It was shown that candesartan cilexetil with natural resveratrol did not lead to functional changes. There were no changes of behavior during the observation period. The combination of candesartan cilexetil with resveratrol did not lead to the death of mice, therefore the mean lethal dose (LD50) was not determined. The new combination of substances was safe. No side effects have been reported. The combination of candesartan cilexetil with resveratrol is non-toxic, and the use of these substances is safe for animals.

Effect of modulation of hydrogen sulfur and glutathione synthesis on oxidative and nitrosative metabolism under myocardial ischemia-reperfusion

Redox balance maintaining is a prerequisite for normal cardiomyocytes metabolism. Reperfusion injury of the heart is characterized by an explosive increase in ROS generation, cell membranes damage, dysfunction of proteins, the development of muscle contracture etc. It was shown that the hydrogen sulfide (H2S) and the precursor of its synthesis the amino acid L-cysteine provided cardioprotective effect against ischemiareperfusion, In addition, L-cysteine is one of amino acids that form an antioxidant glutathione (GSH). The aim of our work was to investigate the effect of GSH and H2S synthesis modulation on the oxidative and nitrosative stress in cardiac tissues under conditions of ischemia-reperfusion. The H2S synthesis inhibitor propargylglycine (PAG), the GSH synthesis inhibitor butionine sulfoxime (BSO) and L-cysteine were administered intraperitoneally. Next, ischemia-reperfusion of the Langendorff isolated rat heart was performed. In the tissues of rat's hearts, before and after ischemia, we determined the rate of ROS generation, content of POL products, the activity of NO synthesizing enzymes. Results of our study showed that pretreatment with PAG + L-cysteine combination prevented heart function disturbances, ROS formation, increased low molecular weight nitrosothiols content, preserved the activity of constitutive NOS and inhibited the activity of inducible NOS in the pre-ischemic period as well as in the period of reperfusion. Pretreatment with BSO in PAG + L-cysteine group significantly reduced the effectiveness of the combination and abolished cardioprotective effect. Generation of superoxide and hydroxyl anions was increased, activity of inducible NO-synthase was 3.5-fold increased comparing with PAG + L-cysteine pretreated group. Pretreatment with PAG + L-cysteine combination inhibited the formation of ROS and preserved the activity of constitutive NOS, thus providing stable production of NO. Pretreatment with BSO completely abolished an antioxidant effect of PAG + L-cysteine decreasing bioavailability of glutathione.

A preliminary information on spider fauna (Arachnida, Aranei) of the Fastiv district (Kyiv region)

In this article, an inventory of the spider fauna of the Fastov district of the Kiev region was carried out, an annotated list of spiders was compiled and includes 84 spider species of 67 genera from 20 families. The annotated list contains faunistic material, collection method and biotopic preferences of species. The most represented by the number of species in the fauna are the families Araneidae – 19 species (24 %), Thomisidae – 8 species (9 %) and Salticidae – 8 species (9 %). The dominance of species of the family Araneidae is due to the large proportion of the surveyed habitats and vegetation layers inhabited by orb weaving spiders. In general, widespread species of spiders with high ecological plasticity were prevail. Including 10 species: Clubiona caerulescens, Harpactea rubicunda, Haplodrassus silvestris, Zelotes electus, Diplostyla concolor, Tenuiphantes flavipes, Agroeca brunnea, Pardosa amentata, Pseudeuophrys erratica and Ozyptila praticola were recorded in the litter layer of a pine forest only. Three species: Cyclosa oculata, Oxyopes ramosus and Dolomedes plantarius are rare according to the literature data. Five species were found in near-water habitats: Larinioides cornutus, Clubiona phragmitis, D. plantarius, Tetragnatha extensa, and Marpissa radiata, and were not found in the other biotopes. Two species, Metellina segmentata and Tetragnatha montana, are found on near-water vegetation and forest edges. In buildings and in household plots, two synanthropic species were found – Tegenaria domestica and Parasteatoda tepidariorum. The zoogeographic and taxonomic compositions of the araneofauna of the region under study are presented. Arealogically, the basis is made up of the Palaearctic (35 %) and Holarctic (19 %) groups. West-Central-Palaearctic species – 14 %, European-Ancient Mediterranean – 12 %. European and more northern European-Siberian species account for 8 and 5 %, respectively. In comparison with the data for Polesie, the araneofauna of the Fastov region has certain characteristics, namely: a large participation in the composition of the araneofauna of Palaearctic and Holarctic species, a decrease in the proportion of EuropeanSiberian species and an increase in the proportion of European-Ancient Mediterranean groups of species.

Certain biochemical aspects of coronavirus infection COVID-19

An outbreak of coronavirus disease CoViD-19, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in a short period of time led to a global public health emergency worldwide. The difficult epidemiological situation associated with the rapid increase in the number of patients and the high mortality rate, as well as the need to overcome the consequences of the pandemic as soon as possible, have become an important challenge for science. The special attention of scientists is focused on in-depth study of the pathogenetic mechanisms of coronavirus infection, which is important for the development of antiviral drugs and vaccines to combat CoViD-19. To penetrate the target cells the virus uses receptors, expressed in various tissues of the organism, the main of which is angiotensin-converting enzyme 2 (ACE2). Virus replication is regulated by a lot of factors and causes abrupt morphological and physiological changes in cells. SARS-CoV-2 disrupts the regulation of inflammatory signaling pathways that generate a cytokine "storm", causes multisystem disorders and a life-threatening condition – acute respiratory distress syndrome. An important component of pathogenesis and clinical manifestations of CoViD-19 are hemostasis disorders, activation of thrombosis and thromboembolic complications. This review provides certain data regarding the structure of SARS-CoV-2, routes of infection, defense mechanisms against pathogen invasion, features of the hemostasis system in coronavirus infection, intracellular signal transduction, and current strategies for the prevention and treatment of CoViD-19, which are aimed primarily at suppressing the replication of the virus, limiting its dissemination and reducing the immune response of organism in conditions of infection.

Study of proteolytic activity in rats kidney and liver during the development of chronic alcoholic intoxication

The study of biochemical processes in chronic alcohol intoxication is a topical issue of our time. A deeper understanding of the mechanism of action of proteinases in this pathological condition will help in the development and search for non-invasive diagnostic methods, thereby minimizing the risk of harming human health during complex diagnostic procedures. In our experiment, we investigated the general proteolytic activity, the activity of metalloproteinases and serine proteinases in the liver and kidneys of rats on an experimental model of chronic alcohol intoxication on days 1, 3, 7, and 11 of the experiment, as well as on days 21 and 28 after the cessation of ethanol administration. Male rats weighing 180–200 g were modeled for chronic alcohol intoxication by intragastric administration of 30% ethyl alcohol solution for 10 days on an empty stomach, at the rate of 2 ml per 100 g of animal weight. Liver and kidney homogenate by well-known methods. The concentration was determined by the Bradford method. The total proteolytic activity, the activity of metalloproteinases and serine proteinases were determined by the caseinolytic method with modifications. The total proteolytic activity, the activity of metalloproteinases and serine proteinases were determined by the caseinolytic method with modifications. It was shown that on the 3rd, 7th and 11th days of the experiment in the liver there was an increase in the total proteolytic activity and the activity of metalloproteinases. The activity of serine proteinases significantly increased on days 3 and 7 of the study. In the kidneys, a significant increase in all studied activities was observed only on the 3rd day. Such differences in the activities of metalloproteinases and serine proteinases can be associated with the different roles of these enzymes in physiological processes. Thus, we observed an increase in the activity of serine proteinases in acute intoxication, and in metalloproteinases in chronic intoxication.

Glutathione system in rat blood serum under the conditions of carrageenan-induced joint inflammation and chondroitin sulfate prophylactic injection

The goal of this work was the research of chondroitin sulfate prophylactic action on the glutathione system state in rat blood serum during acute joint inflammation. The research was performed on white non-linear pubertal rat males weighting 160-240 grams in compliance to all general ethical principles of animal research. All animals were divided to four experimental groups. The first group – the control: the animals were injected with 0,1 ml of 0,9 % NaCl solution in a right hind leg. The second group – rats were subjected to daily intramuscular injections of 3 mg/kg of chondroitin sulfate in the theurapeutic dose during 28 days. The third group – the animals were subjected to daily doses of 0,1 ml of 0,9 % NaCl solution injected in right hind extremities and starting from 29th day the acute joint inflammation was modelled (the animals were subjected to 0,1 ml of 1% of сarrageenan intramuscular injection in right hind extremities. The fourth group – rats were receiving intramuscular injections of therapeutic dose of 3 mg/kg of chondroitin sulfate for 28 days, and after that the acute joint inflammation was modelled starting from 29th day. 40 animals in all were taking part in the experimental research. The glutathione peroxidase activity was assessed judging from the decrease in GSH amount in the reaction with Ellman reagent. The glutathione peroxidase activity was estimated by the decrease in probe optical density owing to NADPH oxidation. Glutathione transferase activity was estimated by the speed of the conjugate formation between GSH and 1-chloro-2,4-dinitrobemzene. The amount of reduced glutathione was estimated spectrophotometrically using orthophthalic aldehyde. It was established that during the carrageenan-induced inflammation the glutathione peroxidase, glutathione reductase and glutathione reductase activity were reduced, a well as the amount of reduced glutathione, whereas the glutathione transferase activity was increased in comparison to the control. It was shown that under the prophylactic injection of the chondroitin sulfate based preparate to animals with acute joint inflammation the aforementioned parameters were partially stabilized.

Spring Ascomycetous fungi (Ascomycota) of the Nature Tract "Kholodnyi Yar"

Information about spring ascomycetous fungi on the territory of the nature tract "Kholodnyi Yar" is presented. As the result of the study 33 species of the ascomycetous fungi were identified, 19 of which are actually spring species and 14 – found in the spring. 15 species are registered for the nature tract "Kholodnyi Yar" for the first time. The largest number of species is represented by the family Morchellaceae (5 species), as well as by the families Pezizazeae (4 species) and Sclerotiniaceae (4 species). The ecological-trophic structure is dominated by species with a saprotrophic feeding strategy, which belong to xylotrophs, humus saprotrophs and herbophilic fungi. The group of xylotrophs was the predominant group of saprotrophic fungi in terms of the number of species (10 species). Humus saprotrophs numbered 9 species of the order Pezizales. In addition, representatives of the group of herbophilic (6 species), which use last year's remnants of herbaceous plants as a substrate, were quite common. Dumontinia tuberosa was the most common species among biotrophic species which parasitizes on the rhizomes of plants of the genus Anemone and forms fruiting bodies at the same time as the flowering period of the host plant. Symbiotrophs were represented by 3 species that are also capable of the saprotrophic feeding strategy inherent to humus saprophytes. A new location for Gyromitra slonevskii, Morchella crassipes and M. steppicola – species which were listed in the third edition of the Red Book of Ukraine – has been registered. Species included in the local red lists were also identified, namely Gyromitra gigas and Verpa bohemica (Kyiv region), Helvella acetabulum (Kherson region). The finding of Phylloscypha phyllogena is the second in Ukraine and the first on the territory of the Right-Bank Forest-Steppe.

Analysis of garden snail (Helix aspersa Muller) mucus for the presence of potential effectors of hemostasis system

Today, there are many approaches to new drugs development, but none of them can replace the important role of natural products in the discovery and development of drugs. Natural raw materials remain an extremely important source of medicines. A number of biologically active molecules of natural origin have already found a direct medicinal use, while many others can serve as chemical models or templates for the design and synthesis of new pharmaceutical agents. Snail mucus has been attracting the attention of scientists for many years as a source of natural biologically active substances. The components of snail mucus have been repeatedly tested for antimicrobial, antioxidant, anti-inflammatory and anti-cancer activities. In this work, the biological effects of components of the mucus of the garden snail Helix aspersa, distributed in Ukraine, were studied. The research results proved the presence of protein molecules, some of which had a pronounced proteolytic potential with specificity for gelatin, collagen and fibrinogen. When mucus was added to blood plasma, its components initiated the formation of active thrombin, and also prolonged the clotting time of plasma in the coagulation test APTT. In addition, the components of H. aspersa mucus enhanced the effect of platelet aggregation inducer and inhibited their disaggregation. It was proved that the components of H. aspersa mucus had no cytotoxic effect. The obtained results indicate the prospects and importance of further experiments on the study of mucus protein fractions in order to identify individual biologically active molecules responsible for the manifestation of these effects. A detailed analysis of the composition and study of the properties of snail mucus will serve as a basis for obtaining potentially new substances with targeted activities and their further use in various industries, including pharmaceutical.

Betaine influence on the endothelial cells

The use of betaine as a bioactive substance remains relevant due to its role in methylation processes (including methionine), antioxidant protection of cells for lipid metabolism, participation in anti-inflammatory processes and stabilization of the endothelial-epithelial barrier as a powerful regulator of metabolic processes in cells and tissues. Therefore, the aim of this work was to study the direct effect of betaine on cultured endothelial cells. The objectives of the work were to analyze the literature on the use of betaine as a donor of methyl groups and osmoprotector (especially the use of its osmotolytic properties), and to conduct experimental studies of its effect on endothelial cells. The effect of betaine on endothelial cells (RAE lines) was studied using traditional methodological approaches: MTT test to determine the activity of mitochondrial enzymes and cell survival, assessment of glucose uptake and morphological properties of endothelial cells. The results of the study of the effect of betaine on endothelial cells showed no toxic effects, increased concentration of endothelial cells compared with control of its level of 0,5 mg/ml and 1 mg/ml when stained with trypan blue, increased optical absorption due to reduction of formazan by mitochondrial enzymes in living cells within its concentrations of 1–4 mg/ml by MTT test, increasing the activity of mitochondrial oxidoreductases per unit of living cells at its concentrations of 1 and 4 mg/ml, the highest absorption of glucose by cells at 0,125 mg/ml and 1 mg/ml of the biological product, compared with the control there were morphological differences of cells, namely: elongation, greater number of processes and the formation of structures that had signs of procapillary. Therefore, betaine at a concentration of 1 mg/ml may serve as a kind of standard of positive effects on endothelial cells in subsequent studies of bioactive drugs.