THE LEVELS OF VISFATIN AND TOLL-LIKE RECEPTORS IN ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS N. Pokrovska, S. Mahiiovych, I. Fomenko, L. Biletska, H. Sklyarova, et al. Ukrainian Biochemical Journal, 2024 Hypertension and type 2 diabetes mellitus (DM) remain widespread diseases that are becoming more prevalent. The role of visfatin and toll-like receptor (TLR) molecules in the pathogenesis of these diseases requires further research. Our aim was to study changes in visfatin and TLR levels in patients with hypertension and type 2 diabetes. Fifty-one patients were examined and divided into two groups: group 1 included 27 patients with hypertension and group 2 included 24 people with hypertension and type 2 DM. The control group included 18 practically healthy people. All individuals underwent general blood test, coagulogram, biochemical blood test, enzyme immunoassay to determine the level of visfatin and TLR in the blood serum and echocardiography. Hypertrophy of the walls of the left ventricle (LV) was observed in patients of two observed groups. The most common type of LV geometry was concentric hypertrophy (41.2%). The level of visfatin was significantly higher in patients of group 1, while in patients of group 2 it was decreased (P ˂ 0.05) and the level of TLR was increased (P ˂ 0.05). The elevated level of TLR in the serum of patients with hypertension can be considered a factor of low-grade inflammation, especially in combination with type 2 DM. The increase in the concentration of visfatin in hypertension serves as a more sensitive marker compared to TLR regarding the risk of developing comorbid cardiovascular pathology. The therapeutic treatments of patients with type 2 DM cause a reduction in the concentration of visfatin induced by hypertension. Keywords: hypertension, toll-like receptors, type 2 diabetes mellitus, visfatin
Galectin-3 in Blood Serum and Lymphocytes as a Marker of Myocardial Damage in Patients with Arterial Hypertension and COVID-19 Nataliia Pokrovska, Nataliia Denysenko, Iryna Fomenko, Helen Sklyarova, Andrii Basylevych, et al. Anti Inflammatory and Anti Allergy Agents in Medicinal Chemistry, 2023 Background:: The constant increase of arterial hypertension and the development of pathology at an earlier age are global healthcare problems that cause damage to vital organs and worsen patient prognosis. In recent years, studies have shown that galectin-3 plays a role in the development and progression of arterial hypertension and coronavirus disease (COVID-19). Objective:: The explanatory research study aimed to analyze the prognostic value of galectin-3 de-termination in the serum blood and lymphocytes of patients with arterial hypertension and corona-virus disease (COVID-19). Methods:: The patients were divided into two groups: Group 1 consisted of 36 individuals with AH, Group 2 included 35 patients with arterial hypertension and polysegmental COVID-19 pneumonia, and 16 practically healthy individuals were included in the control group. All patients underwent anthropometry, biochemical blood analysis, determination of galectin-3, level in serum and lym-phocytes, IL-1β, IL-6, and echocardiography. Results:: The highest level of galectin-3 was found in patients of Group 1, while in patients of Group 2, the concentration of galectin-3 was significantly decreased, mostly due to the treatment of COVID-19, in addition to prolonged antihypertensive therapy. Conclusion:: The level of galectin-3 in serum and lymphocytes was significantly higher in patients of both groups compared to the control group (p<0.05). Arterial hypertension causes structural changes in the cardiovascular system that are associated with elevated levels of galectin-3 in serum and lymphocytes. It can be used as a marker of myocardial damage in the context of arterial hyper-tension and COVID-19.
Investigation of the role of no, Н2 s and the cyclooxygenase/ prostaglandins system in large intestinal mucosa of rats under condition of experimental ulcerative colitis I.S. Fomenko, Т.I. Bondarchuk, A.S. Huet, А.Ya. Sklyarov, and Fiziologichnyi Zhurnal, 2020 The role of gaseous mediators NO and H2S and the cyclooxygenase/prostaglandins system in large intestinal mucosa was investigated in experiments on white rats under condition of experimental ulcerative colitis caused by introduction of acetic acid. Ulcerative colitis was accompanied by the formation of lesions of mucosal barrier of large intestine and the presence of ulcerative defects. The administration of H2S-releasing compound ATB-346 on the background of colitis significantly decreases the area of lesions as compared to naproxen or celecoxib action, that is the most probably caused by the action of H2S. Nonselective cyclooxygenase inhibition by naproxen was accompanied by the decrease of H2S concentration in blood serum and the level of gene Cbs expression in large intestinal mucosa, whereas under the condition of АТВ-346 action the above parameters were close to their normal values. Both naproxen and АТВ-346 decreased the level of gene Nos2 expression and activity of iNOS, which was sharply increased in colitis. Thus, the action of the naproxen derivative H2S releasing compound АТВ-346 is mainly caused by the action of hydrogen sulfide and its influence on іNOS system, and is manifested by a better cytoprotective effect as compared to naproxen action on the background of experimental ulcerative colitis.
Nitroso-oxidative stress after activation of 5-HT4 receptors under conditions of colitis in rats Nataliya Denysenko, Vitaliy Yemelyanenko, Iryna Fomenko, Alexander Sklyarov Current Issues in Pharmacy and Medical Sciences, 2019 Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the regulation of the functioning of the gastrointestinal tract, including that of the colon. The response of smooth muscles, blood vessels and colon mucosa (CM) to 5-HT is realized through the activation of various types of 5-HT receptors, in particular, 5-HT4 receptors, since the latter are identified on colon cells membranes (enterocytes, smooth muscles and endothelium). The aim of our study was to determine the effect of 5-НT4 receptors agonist (mosapride) on nitrogen (II) oxide production and lipid peroxidation in CM and colon muscle tissue (CMT) under the conditions of experimental ulcerative colitis (UC).
Hydrogen sulfide releasing 2-mercaptoacrylic acid-based derivative possesses cytoprotective activity in a small intestine of rats with medication-induced enteropathy Yulia Sklyarova, Iryna Fomenko, Iryna Lozynska, Andrii Lozynskyi, Roman Lesyk, et al. Scientia Pharmaceutica, 2017 Small intestinal injury is known to be one of the most commonly appearing pathologies, resulting in the use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs), antitumor drugs and angiotensin-converting enzyme (ACE) inhibitors. The principal objective of this study is to evaluate the action of a novel mercaptoacrylic acid derivative able to release H2S on parameters of NO-synthase system and oxidative stress. Inducing enteropathy, three types of medications were used: indomethacin, an NSAID (35 mg/kg); methotrexate, an antitumor drug (10 mg/kg); and enalapril, an ACE inhibitor (2 mg/kg/day). 2-[(4-chlorophenyl-carbamoyl)-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-acrylic acid (2C3DHTA) was introduced based on the background of medication-induced enteropathy (10 mg/kg/day). The survey showed that malondialdehyde (MDA) concentration, myeloperoxidase (MPO) activity, superoxide dismutase (SOD), catalase, and NO-synthases (NOS) were determined in the small intestinal mucosa. The increase in inducible NO-synthase (iNOS) activity was due to indomethacin and methotrexate administration. Constitutive NO-synthase (cNOS) activity was decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by 2C3DHTA, which returned iNOS activity to its control level and increased cNOS activity. The enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested, activity of MPO was increased. MPO activity and manifestations of oxidative stress were decreased by 2C3DHTA. Effects of 2C3DHTA can be explained by the action of H2S, released from this compound in the gastrointestinal (GI) system.
Interactions between nitric oxide and hydrogen sulfide generating systems in gastric mucosa under condition of the combined action of stress and NDAIDs I. Fomenko, A. Sklyarov, N. Denysenko, N. Hrycevych, A. Dranitsyna, et al. Journal of Applied Pharmaceutical Science, 2017 Article history: Received on: 29/01/2017 Accepted on: 18/03/2017 Available online: 30/08/2017 The metabolic relationship between H2S and NO in gastric mucosa in norm and pathology is still poorly studied. Aim of this study was to determine mechanisms of interaction between NO and H2S generating systems under conditions of the combined actions of NSAIDs and stress. Water restraint stress (WRS) was used to induce peptic lessions in rats; naproxen and ATB-346 were administered prior to WRS. Nos2, Cbs and Ptgs2 gene expression level was determined by semiquantitative RT-PCR in gastric epitheliocytes. In the gastric mucosa were determined: alterations in H2S and NOx concentrations, changes in activity of myeloperoxidase. Both WRS and naproxen action prior to WRS cased a significant rise in myeloperoxidase activity. Administration of ATB346 resulted in a considerable decrease of myeloperoxidase activity. Naproxen action caused the downregulation of Nos2. The level of Cbs expression in group pretreated with naproxen was much higher than in group of WRS alone. We suppose that it increases as a result of Nos2 downregulation and the correspondent decrease of NO concentration. The relationship between NO and H2S in the gastric mucosa is likely mediated through the regulation of genes expression. As a result of the released H2S, ATB-346 administration decreased the severity of gastric mucosa lesions.
Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs Iryna Fomenko, Tetyana Bondarchuk, Vitaliy Emelyanenko, Natalia Denysenko, Sklyarov Pavlo, et al. Current Issues in Pharmacy and Medical Sciences, 2015 The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS), arginase, cyclooxygenase (COX) and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs) synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX) inhibitor, darbufelone) were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS). WRS brought about an increase of inducible NOS (iNOS) activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS) and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.
Role of cyclooxygenase in modification of intestinal microflora under stress condition Fiziolohichny Zhurnal Kiev Ukraine 1994, 2015
Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis Journal of Physiology and Pharmacology, 2011
Dual acting COX/LOX nonsteroidal anti-inflammatory drugs versus traditional COX-2 inhibitors Annales Universitatis Mariae Curie Sklodowska Sectio Ddd Pharmacia, 2010
The effect of COX-2 inhibitor celecoxib and proton pump blocker lansoprazole on lipoperoxidation processes in heart tissue and gastric mucosa of streptozotocin-induced diabetic in rats Annales Universitatis Mariae Curie Sklodowska Sectio Ddd Pharmacia, 2009
