Nikolay V Goncharov

Nikolay V Goncharov
Sechenov Institute of Evolutionary Physiology and Biochemistry

Professor

About

136
Publications
19,905
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1,242
Citations
Citations since 2017
68 Research Items
888 Citations
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200

Publications

Publications (136)
Article
Full-text available
An increasing number of the population all around the world suffer from age-associated neurodegenerative diseases including Parkinson's disease (PD). This disorder presents different signs of genetic, epigenetic and environmental origin, and molecular, cellular and intracellular dysfunction. At the molecular level, α-synuclein (αSyn) was identified...
Article
Full-text available
Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants,...
Article
Full-text available
The development of drugs for the therapy of COVID-19 is one of the main problems of modern physiology, biochemistry and pharmacology. Taking into account the available information on the participation of mast cells and the role of histamine in the pathogenesis of COVID-19, as well as information on the positive role of famotidine in the prevention...
Conference Paper
Full-text available
In the present study, preclinical testing of the effect of modulators of the ligand-binding and enzymatic properties of albumin on the survival of rats in acute poisoning with organophosphates (OPs) has been performed. According to the obtained data, the application of epigallocatechin gallate (EGCG) as a part of adjuvant therapy promoted the survi...
Article
Full-text available
The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specif...
Article
Full-text available
Being one of the main proteins in the human body and many animal species, albumin plays a crucial role in the transport of various ions, electrically neutral molecules and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind almost all known drugs, many nutraceuticals and toxic substances, determining their pharmaco-...
Article
Full-text available
Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of alb...
Article
Full-text available
Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, la...
Article
Full-text available
— Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes and released into the blood as high molecular weight multimeric glycoproteins weighing up to 20 million Daltons. Blood plasma metalloprotease ADAMTS13 cleaves ultra-large vWF multimers to smaller multimeric and oligomeric molecules...
Article
We studied the effect of different doses of ammonium chloride (ACl) and ammonium carbonate (ACr) on immunological parameters of the peripheral blood in rats during high-intensity exercise. Changes in the absolute and relative numbers of granulocytes, lymphocytes, natural killers, naive and mature effector cells one day after the end of the forced s...
Article
Full-text available
Preconditioning is often used in medicine to protect organs from ischemic damage and in athletes to enhance the performances. We tested whether low-dose ammonium preconditioning (AMP) could have a beneficial effect on physical exercises (PE). We used Cardiopulmonary Exercise Testing (CPET) on a treadmill to investigate the effects of low-dose AMP o...
Chapter
Fatigue during exercise is defined as the inability to maintain the required level of strength and performance. Doping agents and manipulation of any kind are undesirable companions of professional and amateur sports. Nutraceuticals have advantages over medicines because they avoid side effects and naturally supplement the diet. In this chapter, ex...
Chapter
Toxic and mechanistic properties of nutraceuticals are not as extensively studied as those of pharmaceuticals. Flow cytometry is among the most popular techniques to investigate the modes and mechanisms of cytotoxic action of chemical compounds, though flow cytometry methods are not suitable for online registration of rapid changes in cell volumes....
Chapter
Organosulfur compounds (OSCs) are widely present in our bodies and the natural environment. There are two principal groups of vegetables that contain OSC with special properties. Garlic, onion, shallot, leek, and chives are well-known representatives of the Allium genus (family Amaryllidaceae), that contain S-alk(en)yl-l-cysteine sulfoxides. Cabbag...
Article
Full-text available
Here, we propose a new approach for quantitative estimation of von Willebrand factor (vWF) exposed on the surface of endothelial cells (ECs) using the ARC1779 aptamer that interacts with the vWF A1 domain. To visualize complex formation between vWF and the aptamer, the latter was conjugated with the Cy5 fluorescent label. Cultured human umbilical v...
Article
Full-text available
Being one of the most abundant proteins in human and other mammals, albumin plays a crucial role in transporting various endogenous and exogenous molecules and maintaining of colloid osmotic pressure of the blood. It is not only the passive but also the active participant of the pharmacokinetic and toxicokinetic processes possessing a number of enz...
Article
The amount of publications devoted to the endothelial cells, on the one hand, and neurological diseases, on the other hand, has been growing rapidly in recent years. Nevertheless, the relationship between the endothelial monolayer and the cells of the nervous system remains poorly studied. This review presents the available information about endoth...
Article
Full-text available
As a carrier of many biologically active compounds, blood is exposed to oxidants to a greater extent than the intracellular environment. Serum albumin plays a key role in antioxidant defence under both normal and oxidative stress conditions. This review evaluates data published in the literature and from our own research on the mechanisms of the en...
Article
Poisoning with organophosphorus compounds occupy one of the leading places in exotoxicosis. At the first stage, the detoxification of organophosphates can be provided with the help of DNA or RNA aptamers that bind the poison in the bloodstream. Currently, the main method of searching for aptamers is the experimental method of systematic evolution o...
Article
Endothelial cells (ECs) line the blood vessels and lymphatic vessels, as well as heart chambers, forming the border between the tissues, on the one hand, and blood or lymph, on the other. Such a strategic position of the endothelium determines its most important functional role in the regulation of vascular tone, hemostasis, and inflammatory proces...
Article
We compared the effects of two doses of ammonium chloride and ammonium carbonate (10 and 20 mg/kg) on the duration of swimming and blood lactate level. Ammonium chloride in a dose of 20 mg/kg was more efficient than in a dose of 10 mg/kg. The efficiency of ammonium carbonate in a dose of 10 mg/kg was similar to that of ammonium chloride in a dose o...
Article
Finding and studying the mechanisms of action of substances of natural origin that would reduce fatigue and restore the performance of skeletal muscles under extreme physical loads are very important tasks of sports physiology and medicine. A comparison of the effects of decaffeinated green tea extract (GTE) and ammonium chloride (AChl), which we p...
Article
Ammonium, an end-product of catabolism, in low doses can promote adaptation of metabolic pathways in erythrocytes under conditions of extreme physical exercise. We compared the effects of two ammonium salts, ammonium chloride and ammonium carbonate, in two doses on biochemical parameters of rat erythrocytes 1 day after extreme physical exercise in...
Article
The effect of the Cys34 oxidation state in human serum albumin on its binding and catalytic activity towards paraoxon was investigated using molecular modeling methods. Three levels of the cysteine oxidation were considered: (1) Cys34 is reduced, (2) Cys34 is oxidized to sulfenic acid, and (3) Cys34 is oxidized to sulfinic acid. The conformational...
Article
Full-text available
Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic...
Article
Full-text available
In two rat models of acute paraoxon (POX) poisoning against the background of specific and nonspecific inhibition of blood plasma carboxyl esterase (CE) activity, the POX effect on morphology and functions of the rat kidneys was assessed within a period from 1 day to 6 weeks after the poisoning. During the first 3 days, rats developed transient gly...
Article
One of the urgent tasks of clinical toxicology is the development of therapy aimed at stoichiometric and/or catalytic detoxification of organophosphorus compounds in the bloodstream, which will prevent the poison’s entering the neuromuscular and neuronal synapses and help to avoid irreversible consequences of poisoning. An auxiliary option for the...
Chapter
Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables, and fruits. Most of them possess antioxidant or anti-inflammatory properties and are claimed to provide protection against many diseases if taken regularly. At the same time, toxicological studies of nutraceuticals have been limited, so t...
Conference Paper
Full-text available
Проведено морфометрическое исследование мышечных волокон SOL и EDL крыс после цикла принудительного плавания с применением экстракта зеленого чая (ЭЗЧ) и малых доз хлорида (ХА) и карбоната (КА) аммония в контексте изучения эффективности препаратов для снижения мышечного утомления и восстановления мышечной функции. Наиболее значимые изменения после...
Article
Poisoning by organophosphates (OPs) takes one of the leading places in the total number of exotoxicoses. Detoxication of OPs at the first stage of the poison entering the body could be achieved with the help of DNA- or RNA-aptamers, which are able to bind poisons in the bloodstream. The aim of the research was to develop an approach to rational in...
Article
The directional effect on albumin of the molecules which modulate its binding and/or esterase activity could allow stoichiometric and/or catalytic detoxification of organophosphates in the bloodstream. In this study, the effect of polyphenols on binding and catalytic activity of human (HSA) and rat (RSA) serum albumins has been investigated by mole...
Article
Studying the drugs of natural origin that promote recovery of an organism after acute poisoning with household and industrial toxicants, including organophosphates (OPs), is a challenge not only to toxicology but also informatics, which is a major tool for developing the methodology of system analysis. We report here the data on the effect of decaf...
Article
Red blood cells of rats were exposed to the earth’s magnetic field and an attenuated magnetic field in the presence of tert-butyl hydroperoxide to induce oxidative stress. Spectral analysis within the wavelength range of 500–700 nm was used to estimate the concentration of three forms of hemoglobin: oxyhemoglobin, methemoglobin, and hemichrome, rel...
Article
The long-term effects of acute organophosphate (OP) poisoning remain poorly studied, while experimental models usually disregard species-related specificity of rodents as model objects. Here we present two toxicological models and a comparative analysis of a wide range of biochemical blood indices in their dynamics over 3 months after acute rat poi...
Article
Full-text available
In this study, we investigated the effects of NAD(P)H oxidase (NOX) inhibitor VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine) on the histamine-induced elevation of free cytoplasmic calcium concentration ([Ca2+]i) and the secretion of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs) and on rela...
Article
Full-text available
Hydrogen peroxide, formed in the endothelium, acts as a factor contributing to the relaxation of blood vessels. The reason for this vasodilatory effect could be modulation by H 2 O 2 of calcium metabolism, since mobilization of calcium ions in endothelial cells is a trigger of endothelium-dependent relaxation. The aim of this work was to investigat...
Article
Full-text available
Isoform H of acetylcholinesterase (AChE) is located on the outer surface of erythrocytes; its inhibition with organophosphorus compounds (OPC) may impair structural and functional properties of erythrocytes. The aim of this study was to elucidate the effects of paraoxon (POX) on the osmotic resistance, the level of reactive oxygen species (ROS), in...
Article
Full-text available
The effects of hydroquinone (200 mg/kg) on spontaneous periodic motor activity (SPMA) and a number of biochemical markers were studied in 116-day-old rats. According to Laborit (1965), the mechanism of hydroquinone action is based on inhibition of the pentose phosphate pathway in excitable structures. Herein, we confirmed that intraperitoneal injec...
Article
The currently existing terms “apoptotic index” and “apoptotic potential” are insufficient for the adequate qualitative evaluation and analysis of the proapoptotic activity of chemical agents within the wide range of therapeutic and toxic doses. Herein we introduce a new concept of cytotoxic power as an alternative to these terms related to apoptosi...
Article
Currently existing terms "apoptotic index" and "apoptotic potential" are insufficient for adequate qualitative evaluation and analysis of proapoptotic activity of chemical agents within the wide range of therapeutic and toxic doses. Herein we introduce a new concept of cytotoxic power as an alternative to these terms related to apoptosis and other...
Article
Full-text available
Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneo...
Article
We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed a...
Article
Full-text available
The aim of our research was to study the influence of hydrogen peroxide on the exocytosis of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVEC). We have found that H2O2 at a non-toxic concentration (100 μM) increases the amount of vWF secreted by HUVEC by 43 ± 14% over control (p < 0.03) and elevates total exposition of v...
Article
The expression of genes responsible for the synthesis of essential proteins regulating the calcium-ion balance and ultrastructural characteristics of fast-twitch (m. extensor digitorum longus, EDL) and slow-twitch (m. soleus, SOL) skeletal muscles under prolonged exercise were studied in an experimental model of forced-swimming rats. A day after th...
Article
Full-text available
Albumin is known as being able to cleave ester bonds in organophosphates (OP) and serve as a major means of OP detoxification due to its large amount in the blood serum. Most of in vivo toxicological studies are conducted on rodents, mice and rats. To adequately extrapolate results of ligand/albumin interaction studies to a human organism, it is ne...
Article
New β-diazopyrrole and β-triazenylpyrrole derivatives were synthesized from isoxazoles and pyridinium salts in two and three steps, respectively. The apoptotic/necrotic difference for these compounds was estimated on THP-1 cell line. The most effective of the panel is methyl 3-diazo-2-(2,4-dimethylphenyl)-4-phenyl-3H-pyrrole-5-carboxylate which dem...
Article
Full-text available
The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic...
Article
It is known that albumin can break the ester bonds in organophosphorus compounds (OPs). Amino acids responsible for esterase and pseudoesterase activity of albumin towards OPs are still not determined. It is assumed that Sudlow’s site I with residue Tyr150 exhibits the “true” esterase activity; and Sudlow’s site II containing residue Tyr411, a pseu...
Article
Enzymatic activities of three types of serum albumin—rat, bovine and human—were analyzed comparatively using a mathematical model. Kinetic and equilibrium constants of carboxylesterase and paraoxonase activities of albumin in Sudlow’s sites I and II were determined. The effects of specific ligands, ibuprofen and warfarin, on enzyme kinetics in thes...
Article
For the first time, the chronic inhalation effect of aliphatic hydrocarbons (HC) in low concentrations on metabolic profiles of low molecular weight organic compounds including free (FFA) and esterified (EFA) fatty acids in rats brain and liver was studied. Gas and liquid chromatography-mass spectrometry was used as analytical methods. The list of...
Article
The effect of the Pelixim antidote on the possibility to detect markers of G type nerve agents sarin and soman was studies in bio probes obtained in an acute in vivo experiment after exposure of rats to organophosphorus nerve agents in doses of 0.5LD50. It was found out that the intake of equitoxic doses of soman and sarin leads to a decrease of ac...
Conference Paper
Full-text available
После острого отравления фосфорорганическими соединениями (ФОС) в организме происходит развитие ряда неблагоприятных физиологических событий, являющихся следствием «холинэргического криза», в том числе развитие эпилептического статуса и повреждение ЦНС. Поскольку экспериментальные токсикологические исследования проводятся в основном на грызунах, не...
Article
Hydrogen peroxide at concentrations below cytotoxic ones causes an increase in the cytoplasmic calcium concentration in human umbilical vein endothelial cells as a result of calcium release from intracellular stores. Two-pore calcium channel blocker trans-NED19 partially suppresses the increase in the level of calcium ions in the cells in response...
Article
Albumin is known to be able to cleave ether bonds in organophosphates (OPs). Amino acids responsible for esterase and pseudo-esterase albumin activity towards OPs are not yet finally identified. Presumably, Sudlow’s site I with the Tyr150 residue shows a “true” esterase activity, while Sudlow’s II site with the Tyr411 residue—a pseudo-esterase one....
Article
Glycosaminoglycans (GAGs) in the urine of Wistar rats, and on the surface of the epithelium and lamina propria of the bladder, were quantitatively assessed before and after acute intoxication with paraoxon or cyclophosphamide. Paraoxon was administered subcutaneously (s.c.) twice with an interval of 1 h to a final dose of 275 µg/kg; cyclophosphamid...
Article
The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalation exposure to low doses of aliphatic hydrocarbons (HC) with the number of carbon atoms from 6 to 10. The metabolic profile was determined by a combination of gas chromatography/mass spectrometry and high-performance liquid ch...
Article
Full-text available
Isoform H of acetylcholinesterase (AChE) is expressed on the outer surface of erythrocytes, and when it is inhibited by organophosphates, structural and functional properties of erythrocytes can be impaired. The object of this study was to elucidate the mechanisms of the paraoxon (POX) effect on the osmotic resistance, the level of reactive oxygen...
Chapter
Organosulfur compounds (OSC) are widely present in our bodies and the natural environment. There are two principal groups of vegetables that contain OSC with special properties. Garlic, onion, shallot, leek, and chives are well-known representatives of the Allium genus (family Amaryllidaceae) that contain S-alk(en)yl-l-cysteine sulfoxides. Cabbage,...
Chapter
Fatigue during exercise is defined as the inability to maintain the required level of strength and performance. Doping agents and manipulation of any kind are undesirable companions of professional and amateur sports. Nutraceuticals have an advantage over medicines because they lack side effects and naturally supplement the diet. In this chapter, e...
Chapter
Toxic and mechanistic properties of nutraceuticals are not as extensively studied as those of pharmaceuticals. Flow cytometry is among the most popular techniques to investigate the modes and mechanisms of cytotoxic action of chemical compounds, although flow cytometry methods are not suitable for online registration of fast changes of cell volumes...
Article
In blood vessels, serotonin 5-HT2B receptors mainly mediate relaxation, although their activation by the selective agonist BW723C86 is known to exert contraction of aorta in deoxycorticosterone acetate (DOCA)-salt and N(omega)-nitro-L-arginine (L-NAME) hypertensive rats [Russel et al., 2002; Banes et al., 2003] and in mice with type 2 diabetes [Nel...
Article
The reaction of a diazoacetate-derived rhodium carbenoid with azirines or isoxazoles followed by a cyclization-hydrodebromination cascade provides dihydroazetes via formation of 2-azabuta-l,3-dienes.
Article
The blocker of two-pore channels trans-NED19 and hydrogen peroxide were found to inhibit histamine-induced relaxation of rat aorta. The degree of inhibition depended on histamine concentration. The relaxation in response to 1 µM histamine of rat aorta preconstricted with 30 mM KCl, serotonin, or endothelin-1, was completely abolished by 30 µM trans...
Article
A general and concise approach to thermally and hydrolytically stable alkyl 2,3-dihydroazete-2,3-di-/2,2,3-tricarboxylates from alkyl 2-bromoazirine-2-carboxylates or 4-bromo-5-alkoxyisoxazoles is reported. The synthesis involves the formation of 2-azabuta-1,3-diene by the reaction of rhodium carbenoid with isoxazole or azirine followed by cyclizat...
Article
Human umbilical vein endothelial cells were exposed in culture to hydrogen peroxide (H2O2), keeping them close to physiological conditions (high cell density, high serum content, H2O2 concentration not over 500 µM). Cell viability was assessed by flow cytometry using simultaneous staining with the fluorescent dye PO-PRO-1 to detect early apoptotic...
Article
Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са2+ responses to cell proliferation an...
Article
Full-text available
The review considers the development of a new science—metabolomics. The metabolome is mainly regarded as a set of primarily biochemical parameters, each of which or their ratio can serve as a potential biomarker that increases the sensitivity and/or specificity of diagnostics of diseases.
Article
The work was aimed to find new screeding parameters (biomarkers) for evaluation of health state of workers engaged into enterprises with hazardous work conditions, as exemplified by "Maradykovskyi" object of chemical weapons extinction. Analysis of 27 serum cytokines was conducted in donors and the object personnel with various work conditions. Fin...