Iryna Fomenko

RESEARCH, TEACHING, or OTHER INTERESTS

Biochemistry, Clinical Biochemistry, Molecular Medicine, Oncology

Scopus Publications

Efficacy of thiazole derivatives against colorectal cancer induced by dimethylhydrazine in male Wistar rats
Iryna Fomenko, Nataliia Denysenko, Iryna Lozynska, Mariana Kuryk, Ihor Yushyn, Ostap Myhal, Roman Pinyazhko, Andrii Lozynskyi, and Roman Lesyk
Elsevier BV



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, L. Kobylinska, , , ,et al.
National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka) (Publications)
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, Eugene Sklyarov, Sandor G. Vari, and Lesya Kobylinska
Bentham Science Publishers Ltd.
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.


Anti-inflammatory hydrogen sulfide-releasing agents with reduced gastro- And enterotoxicity on the stress model in rats
Iryna FOMENKO, Iryna LOZYNSKA, Tetyana BONDARCHUK, Natalia DENYSENKO, Roman LESYK, and Alexander SKLYAROV
Edizioni Minerva Medica



Investigation of the role of no, Н<inf>2</inf> 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
National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka)
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-HT<inf>4</inf> receptors under conditions of colitis in rats
Nataliya Denysenko, Vitaliy Yemelyanenko, Iryna Fomenko, and Alexander Sklyarov
Walter de Gruyter GmbH
Abstract 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, and Alexandr Sklyarov
MDPI AG
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 and J. Wallace
Journal of Applied Pharmaceutical Science
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, Iryna Ilkiv, Roman Lesyk, and Alexander Sklyarov
Walter de Gruyter GmbH
Abstract 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




Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage
Iryna Fomenko, Alexander Sklyarov, Tetyana Bondarchuk, Lilya Biletska, Natalia Panasyuk, and John L. Wallace
Informa UK Limited
Abstract Mechanisms of gastric defence under conditions of combined influence of acute stress and non-steroidal anti-inflammatory drugs (NSAIDs) are still poorly studied. The aim of this study was to explore the effects of different types of NSAIDs (naproxen, celecoxib and ATB-346) in producing experimental gastric lesions (induced by water-restraint stress (WRS) or by epinephrine (EPN) injection) and to determine the role of lipid peroxidation and the nitric oxide (NO) system in the pathogenesis of the damage. Male rats were used (eight per group) in this work. The NSAIDs were all administered at a dose 10 mg kg−1 30 min prior to WRS or EPN injection. Administration of naproxen to the control rats caused development of gastric lesions, whereas administration of a hydrogen sulfide (H2S)-releasing NSAID (ATB-346) or a selective cyclooxygenase-2 inhibitor (celecoxib) did not cause gastric damage. In contrast, lipid peroxidation processes were enhanced in all groups as was the activity of NO synthase (NOS). Pretreatment with naproxen in the WRS model caused an increase in severity of damage and a decrease in NOS activity. ATB-346 displayed beneficial effects, manifested by a decrease in the area of gastric damage, but parameters of lipid peroxidation and the NOS system did not differ substantially from those in the group treated with naproxen. Administration of different NSAIDs under conditions of EPN-induced gastric damage resulted in the decrease in NOS activity and lipid peroxidation. None of the tested NSAIDs exacerbated EPN-induced gastric mucosal injury; indeed, they all reduced the extent of damage.


[Parameters of NO synthase system of gastric mucosa in rats under stress conditions and inhibition of cyclooxygenase].
IS Fomenko, , TI Bondarchuk, LP Bilets'ka, NB Panasiuk, OIa Skliarov, , , , and
National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka)
In experiments on rats with modeled water-restrained stress, the influence of nonsteroidal anti-inflammatory drugs of different genesis on morphological status of gastric mucosa and changes of NO-synthase system parameters have been studied Administration of nonselective cyclooxygenese inhibitor naproxen in the water-restrained stress model in rats potentiated the increase of severity of damage of gastric mucosa. At the same time, the activity of both inducible and constitutive isoforms ofNO-sythase decreased. The parameters of lipoperoxidation remained at the level observed during water-restrained stress. It was shown the advantages of the use of H2S-releasinfg nonsteroidal anti-inflammatory drug ATB-346, which are associated with its cytoprotective effect of the drug manifested by a decreased total area of gastric damage. However, parameters of lipoperoxidation and NO-syntase system did not differ substantially from those in the group treated with napoxen, indicating the prevalence of parent molecule (naproxen) in regulation of function of NO-system Administration of dual COX/LOX inhibitor, the compound 2A5DHT, caused a decrease of gastric damage as compared to the effect ofnaproxen. The activity of iNOS remained much higher than under condition of the naproxen action.


The role of cyclooxygenase isoforms in the mechanisms of cytoprotection of gastric mucosa under the influence of hexapeptide Arg-α-Asp-Lys-Val-Tyr- Arg
Christina Nasadyuk, Natalya Panasyuk, Iryna Fomenko, and Olexandr Sklyarov
Medical University of Lublin
In experimental epinephrine-induced gastric lesions in rats it was shown that olygopeptide Arg-α-Asp-Lys-Val-Tyr-Arg exerts cytoprotective effect, evaluated by the decrease of the area and severity of the damage of gastric mucosa as well as decrease of NOS activity, mainly due to the decrease of iNOS and NO production in gastric mucosa. Selective COX-2 blockade enhanced the cytoprotective action of AALVTA. Nonselective blockade by COX-1 caused significant decrease of the gastroprotective properties of AALVTA, showing involvement of COX-1 isoform in the mechanisms of cytoprotection of GM under the action of this hexapeptide.


The changes of NO-synthases activity, nitrogen oxide content and lipoperoxidation processes in stomach and colon under conditions of streptozocin-induced hyperglycaemia
Ostap Detsyk, Iryna Fomenko, and Olexandr Sklyarov
Medical University of Lublin
In rats with streptozocin-induced hyperglycaemia the changes of nos activity, nitrite anion content and lipoperoxidation processes in mucous and muscular layers of the stomach and large intestine were studied. It has been showed that hyperglycaemia induces the decrease of cnos activity in mucous layer, while its activity in muscular layer of the stomach and large intestine did not change significantly and іnos activity increased in muscular layer of the stomach and large intestine. Nitrite anion content did not change significantly. Hyperglycaemia caused an increase of the lipoperoxidation processes in mucous and muscular layers of the large intestine; simultaneously sod activity in mucous and muscular layer increased.


Dopamine receptor type 1 of Caenorhabditis elegans expressing in mechanosensory neurons
V. V. Stadnyk, A. Regosh, C. Y. Mayor, I. S. Fomenko, T. I. Bondarchuk, and O. Y. Sklyarov
Institute of Molecular Biology and Genetics (NAS Ukraine)
Until now the results on profiling dopamine receptors in C. elegans have been incomplete and fragmentary. The aim of this study was to investigate the expression profile of dop-1 gene in C. elegans using 3 kb promoter with 3'-end locating before ATG of dop-1gene. Methods. The strain of C. elegans with mutant unc-119 gene was used. To check a pattern of the dop-1 expression, the promoter of this gene was amplified using PCR. The animals were co-bombarded with plasmid pPD95.77 dop-1::GFP and reporter construct containing unc-119 gene. Results. Using GFP as a reporter protein, we built a whole picture of expression of dopamine receptor type 1 in C. elegans and found that this protein could be detected only in mechanosensory neurons such as PLM, PVQR, PVQL, ALNR, ALNL, DVAR, DVC.


Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis




Comparison of dual acting drugs and conventional NSAIDs towards parameters of NO-synthase system and oxidative stress in mucosal membrane of large intestine of rats with experimental ulcerative colitis
A. Ya. Sklyarov, R. B. Lesyk, N. B. Panasyuk, I. S. Fomenko, and D. Ya. Havrylyuk
Institute of Molecular Biology and Genetics (NAS Ukraine)
Aim was to compare the action of 2A5DHT compound (dual COX-2/5-LOX inhibitor) and conventional non-steroidal anti-inflammatory drugs towards parameters of nitric oxide (NO) system and intensity of oxidative stress in the mucous membrane of the large intestine (MMLI) in rats with experimental ulcerative colitis. Methods. Ulcerative colitis was induced by administration of acetic acid. The activity of NOsynthases, content of NO, and parameters of lipoperoxidation processes were measured in MMLI. Results. COX-2/5-LOX inhibition by 2A5DHT compound did not cause considerable destructive changes of the MMLI of rats. The activity of inducible nitric oxide synthase (iNOS) declined more than 2 fold as compared to their activity in colitis. The intensity of lipoperoxidation processes was found to be much lower than under the separate effect of celecoxib or indomethacine. Conclusions. Dual COX-2/5-LOX inhibition by 2A5DHT has a significant cytoprotective effect in MMLI that is accompanied by reduction of oxidative stress and activity of NO-synthases. The substance 2А5DHT significantly overexceeds the cytoprotective effects of both selective and non-selective COX/LOX inhibitors and can be used in the treatment of inflammatory bowel disease.


Dual acting COX/LOX nonsteroidal anti-inflammatory drugs versus traditional COX-2 inhibitors




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