Free Radical Lipid Oxidation Research Articles

Корекція пробіотиком пародонтального синдрому у тварин за умов ожиріння і хронічного стресу

The aim of this study was to investigate the effect of obesity and chronic stress on periodontal tissues, both separately and in the combined comorbidity of these conditions in rats, and the role of the probiotic Lactobacillus casei in the correction of periodontal syndrome under these conditions. Methods. The development of periodontal syndrome and the effectiveness of the probiotic Lactobacillus casei IMV B-7280, administered to rats from one month of age intragastrically in a volume of 1 mL (5 · 108 CFU) in two-week courses with breaks of 2 weeks, were studied in a model of glutamate-induced obesity and chronic stress - in combination and separately. In periodontal tissues, the total proteolytic and antitryptic activity, free fucose and glycosaminoglycans (GAG) content, catalase activity, thiobarbiturate active products (TBA reagents), and the content of oxidatively modified proteins (OMP) and molecules of average mass (AMM) were determined; in bone tissue, the molar root exposure coefficient was calculated. The anthropometric parameters of the animals and the Selye triad were studied. Results. We have substantiated the development of periodontal syndrome in animals with glutamate-induced obesity against the background of chronic stress, as evidenced by the activation of free radical oxidation of lipids and proteins, depolymerization of fucoproteins and proteoglycans of periodontal connective tissue, which causes exposure of molar roots by almost 65%. The administration of the probiotic Lactobacillus casei in two-week courses with intervals of 2 weeks to obese rats with chronic stress prevented the development of obesity, as evidenced by a significant decrease in visceral fat mass, Li index, and BMI, as well as the severity of stress syndrome, as evidenced by a decrease in ulcer formation, thymus involution, and adrenal hypertrophy. The periodontoprotective effect of Lactobacillus casei under the combined influence of obesity and chronic stress was proved by significant changes in oxidative stress, free fucose, and GAG content and a 1.5-times decrease in the molar root exposure ratio. Conclusions. Periodic administration of Lactobacillus casei to rats treated with sodium glutamate in the neonatal period against the background of chronic stress prevented the development of obesity, the severity of stress syndromeб and damage to periodontal tissues, as evidenced by the prevention of oxidative stress, increased catabolism of extracellular connective tissue proteins and antiresorptive effect.

Original Empirical Research Protective Effects of Succinic Acid upon Exposure to the Low-Frequency Alternating Magnetic Field Determined in the Experiment

Introduction. The need to simulate the oxidative stress by an experiment of exposure to the low-frequency alternating magnetic field is induced by the persistent increase of the electromagnetic load on the endothermic organisms caused by the annual deterioration of the electromagnetic state of the environment. The low-frequency alternating magnetic field starts a chain of biochemical reactions in the laboratory animals, which alter the homeostasis against the increased intensity of free-radical oxidation (peroxidation) of biomembrane lipids. The preparations containing succinic acid have the antioxidant, antihypoxant, actoprotective and stress-protective effects, tested through various kind of modelling, however, the absence of data on the efficacy of succinic acid under the exposure to the alternating magnetic field has become the reason for the present experiment. The aim of the research is to determine the protective effects of succinic acid upon exposure of the laboratory rats to the low-frequency alternating magnetic field.Materials and Methods. The objects of the research were 90 white outbred male rats weighing 200–250 g, divided into three groups: group 1 — intact, the animals were in standard vivarium conditions and were not exposed to any effect; group 2 — control, the rats were exposed to the low frequency alternating magnetic field (LF-AMF) for 21 days daily per 3 hours, preceded by daily intraperitoneal administration to animals of the 0.9% sodium chloride solution at a dose of 1 ml / kg straight before them being exposed to LF-AMF; group 3 — experimental, the rats were daily intraperitoneally administered the succinic acid at a dose of 100 mg / kg (1 ml / kg) for 21 days prior to being exposed to LF-AMF. The exposure to the low-frequency alternating magnetic field was created by the Helmholtz coils (of diameter 1 m) powered by the alternating current source with a frequency of 50 Hz, with a magnetic field induction of 0.4 mT, whereas the cages with animals were placed in the centre of the device. The actoprotective effect of succinic acid was checked on the 7th, 14th and 21st days from the beginning of the experiment by duration of swimming of rats in water. The antioxidant effect — by concentration of diene conjugates, lipid hydroperoxides, malondialdehyde, ceruloplasmin, vitamin E in the blood plasma of rats measured according to the commonly accepted methods. The stress-protective effect was determined by the masses of the adrenal glands, thymus gland, spleen and the number of erosive defects on the suRussian Federationace of the gastric mucosa.Results. The experimental data has confirmed the actoprotective effect of succinic acid — the duration of swimming of the rats in the experimental group increased by 25–37% compared to the control one. The antioxidant effect of succinic acid under magnetic induction has been manifested in a decreased concentration of lipid peroxidation products against increased level of ceruloplasmin in the blood of rats in the experimental group compared to the animals in the control group. Administration of the succinic acid into the peritoneum of rats in the experimental group under exposure to the low frequency alternating magnetic field has prevented involution of the thymus gland by 45% (7th day), 56% (14th day), 71% (21th day) and the spleen by 52%, 58% and 66% respectively, alongside, the number of erosive and ulcerative defects on the suRussian Federationace of the gastric mucosa has decreased by 2.5–4 times compared to the animals in the control group.Discussion and Conclusion. The protective effects of succinic acid upon exposure to the low-frequency alternating magnetic field have been confirmed that include the stress-protective, actoprotective and antioxidant effects of the exogenous succinate. The ability of succinic acid to prevent the negative changes in the internal organs caused by the magnetic loads is proved by the statistically significant excess of the mass coefficients of the thymus gland and spleen in the experimental group, compared to the control one, along with the fewer erosive defects on the suRussian Federationace of the gastric mucosa. Succinic acid reduces the intensity of lipid peroxidation processes upon the magnetic exposure due to reducing the concentration of lipid peroxidation products and increasing the level of ceruloplasmin in the blood of animals.

Alcoholic cardiomyopathy: aspects of pathogenesis and clinic

Alcoholic cardiomyopathy is the most common form of myocardial damage caused by ethanol. Ethanol and its main active metabolite acetaldehyde have a direct toxic effect on the myocardium. The mechanisms of the cardiotoxic effect of ethanol are diverse and include membranotropic action, damage to cellular organelles, activation of lipid peroxidation, and a number of others. Dissolving in the lipids of biological membranes, ethanol changes their physico-chemical properties, disrupts the activity of membrane receptors, eventually disconnecting the connection of excitation with the contraction of cardiomyocytes. Particular importance in the pathogenesis of alcoholic cardiomyopathy is attached to the ability of ethanol to cause structural and functional changes in mitochondria, which is directly related to the violation of oxidative processes and energy supply of the myocardium as a whole. Under the influence of alcohol, free-radical lipid oxidation products content increases and antioxidants activity decreases, which indicates oxidative stress development. The deterioration of myocardial contractility due to chronic alcohol intoxication triggers a cascade of compensatory mechanisms in the form of cardiomyocyte hypertrophy and progressive fibrosis, while adaptive reactions become a factor in further pathological changes. Ethanol causes myocardial damage in a dose-dependent manner.The probability of alcoholic cardiomyopathy occurrence is a derivative of the total accumulated dose of alcohol and individual predisposition. Alcoholic cardiomyopathy is considered as a variant of secondary dilated cardiomyopathy with all its clinical manifestations and consequences: dilation of the heart chambers, low left ventricular ejection fraction, progressive circulatory insufficiency, and cardiac arrhythmias. A relatively favorable prognosis in alcoholic cardiomyopathy is provided due to partial reversibility of myocardial damage under the condition of abstinence from alcohol consumption. Specific drugs for the treatment of alcoholic cardiomyopathy have not been developed. New treatment strategies include the use of myocardial growth and regulation factors synthesized by cardiomyocytes, as well as the stimulation of heart muscle regeneration and repair processes.

КОМПЛЕКСНАЯ ОЦЕНКА ЭФФЕКТИВНОСТИ СИСТЕМЫ КОРМЛЕНИЯ ВЫСОКОПРОДУКТИВНЫХ КОРОВ С ИСПОЛЬЗОВАНИЕМ ЖИДКОЙ ЭКД

Due to on black-and-white cows scientific-and-economic experience, the liquid energy feed additive (EKD) feeding’s scheme and technology have been worked out. An integrated assessment conducted during this additive’s testing of the animals’ metabolic processes positive changes in the physiology and biochemistry and health improving had showed. The EKD using in the cows highyielding nutrition during transition period in order to the ration’s energy nutritional value increasing had a positive effect on milk chemical composition, physical and technological properties at average daily milk yield natural fat content of 31,1 and 31,8 kg; 33,3 and 33,2 kg for cows of control and experimental groups respectively, at the 1-st and 2-nd month of lactation. At milk of 4% fat composition counting, the daily milk yields’ average differences was increased and amounted, respectively, 38,0 and 33,8 kg in the control; in the experiment 39,1 and 38,5 kg at the 1-st and 2-nd month of lactation. In the cows milk treated with EKD, the average fat content for 2 months of lactation was 4,8%, protein - 3,5%, versus 4,5% and 3,0%, respectively in controls. This allowed as additional 6,9 kg of fat and 9,4 kg of protein per 1 head during this period obtaining, that was in 8,0% and 16,3% more than in the control groups respectively. The cows milk with EKD receiving was differed positively both in acidity in °T according to Kabyshev, and in thermal stability, rennet-fermentation sample and it had in 2,3 times fewer somatic cells. At the same time, the EKD gave the intensity of protein, carbohydrate and fat metabolism increasing, negatively the functional state of the liver and free radical oxidation of lipids in the first month of lactation with a significant improvement in this condition in the second affecting. The inclusion of dry and newbodied EKD in the cows’ rations is physiologically and economically feasible.

Cronassial Ameliorates Autoimmune Encephalomyelitis by Inhibiting Lipid Oxidation and Carbonyl Stress in the Brain and Spinal Cord of Rats.

In recent years, the pathogenetic role of oxidative stress in damaging myelin cells, a precursor to the development of myelin-related diseases such as multiple sclerosis, has gained increasing significance. Experimental autoimmune encephalomyelitis (EAE) in rats serves as an experimental model for human multiple sclerosis. Our study elucidates and demonstrates the antioxidant properties of Cronassial, a drug containing gangliosides, on the processes of free radical lipid oxidation and oxidative modification of proteins in the brains and spinal cords of rats with EAE. Our research results reveal an elevated production of oxidative stress products, including peroxides, hydroperoxides, and oxidized proteins, in experimental animals. This phenomenon is one of the factors contributing to myelin damage. Administering a ganglioside-containing drug normalizes the consequences of oxidative stress and inhibits the formation of reactive oxygen species. Consequently, the data obtained highlight the neuroprotective and antioxidant effects of Cronassial when administered to animals with autoimmune encephalomyelitis.

Эффективность влияния пребиотической кормовой добавки на продуктивность, антиоксидантную защиту и иммунологический статус кур

Purpose. The study of the productive traits of chickens when fed with a prebiotic supplement that stimulates the antioxidant and immunological defenses of the body Materials and Methods. The studies were carried out in certified laboratories. The resulting digital material was processed using the statistical package Microsoft Excel, which provides verification of the reliability of the data using the Student's criterion. Results. It has been established that the introduction of the feed additive "LactuSuper" into the diet of laying hens of the Hisex Brown cross dramatically increases their productivity by 85 eggs in 10 weeks of the experiment, or by 1.2 eggs per positive laying hen, the egg-laying intensity – by 1.74%, feed savings – by 0.6 g per day per head, obtaining a hatching egg yield of 4% (97% compared to 93% of the control group). The balance of the feed additive "LactuSuper" with biologically active absorbed absorbable carotenoids in the yolk of the incubation eggs of the experimental group was 23.36% (P≤0.001), which was 16.9 µg/g in absolute values. Incubation of eggs showed a high hatch of chickens in both groups (82.44 and 85.27%), but in the experimental group, the excess in this indicator was 2.83%. High rates of production and quality of hatching eggs in the experimental group, apparently, are provided by the activation of metabolism in the body of chickens, as a result of feeding them the studied additive. Due to the antioxidant properties of the tested feed additive the activity of superoxide dismutase (SOD) increased by 11.22% (P≤0.01), glutathione peroxidase (GPO) – by 3.02% (P≤0.05), ceruloplasmin (CP) – by 16.58% (P≤0.01), total antioxidants (TOA) by 26.97% (P≤0.01), and malondialdehyde (MDA) activity decreased by 14.15% (P≤0,01). The level of T-lymphocytes responsible for cellular immunity increased by 12.61% (P≤0.01), and the content of B-lymphocytes characterizing humoral resistance increased by 6.83% (P≤0.05) relative to the control. An increase in the level of classical antibodies was recorded in the experimental group. Thus, the content of IgA and IgG increased by 17.26 (P≤0.01) and 7.62% (P≤0.05) compared with the control. The presence of IgM also exceeded the control values in the experimental group by 7.79% (P≤0.05). Conclusion. Thus, it was found that the feed additive "LactuSuper" developed by us contributed to the increase in the egg production of the parent flock and the quality of hatching eggs. The active substances of the prebiotic supplement ensured a decrease in the level of free radical lipid oxidation, which had a positive effect on the formation of the body's antioxidant defense, strengthening cellular and humoral immunity.

Study of the Chemical Composition and Biological Effects of Aromatic Waters in a Comparative Aspect

Introduction. Vegetable raw materials processing products are becoming very popular. Of particular value are the products of essential oil production – aromatic waters or hydrolates. Hydrolates are widely used as cosmetics because they contain a number of biologically active water-soluble components of essential oil, but unlike the latter they have a softer effect on the skin, which allows them to be used in their pure form.Aim. To study the chemical composition, antibacterial and antioxidant activity of hydrolates.Materials and methods. Hydrolates were used as objects of research of production JSC "AEMSZ" derived from plants: Lavandula angusifolia, Hyssоpus officinаlis, Sаlvia officinаlis, Rosmarinus officinalis, Rosa damascеna × Rosa gallica. The composition was analyzed by gas-liquid chromatography. Antibacterial properties of hydrolates were studied with the use of bioluminescent marine bacteria Aliivibrio fischeri F1 and recombinant test-bacteria Escherichia coli MG1655 (pXen7). The study of the antioxidant effect was carried out by the method of Fe3+-induced lipid peroxidation of egg lipoprotein suspension in vitro.Results and discussion. It was found that salvia hydrolate contains α- and β-thujone, β-caryophyllene, α-terpineol; lavender hydrolate – camphene, linalool, linalyl acetate, geraniol, geranyl acetate; rosemary hydrolate – camphene, 1,8-cineol, β-pinene; rose hydrolate – phenylethanol, geraniol, citronelol, nerol; hydrolate hyssop – pinocamphone, isopinocamphone, spatulenol, β-caryophyllene. The antibacterial properties of the studied hydrolates were manifested in the inhibition of test bacteria bioluminescence and growth. Hydrolates of hyssop, lavender and rosemary were characterized by the greatest activity, rose and salvia had a lesser effect. It was also shown that hyssop and lavender hydrolates exhibited the bactericidal properties. Through the studying the antioxidant effect, the dynamics of accumulation of products of free-radical oxidation of lipids was observed, which in the presence of hyssop and rosemary hydrolates decreased by 40 and 36 %, respectively, in comparison with the control.Conclusion. As a result of the research, it was found that the studied hydrolates have pronounced antibacterial properties. Antioxidant properties of Hyssopus officinalis and Rosmarinus officinalis hydrolates were also revealed. Prospects for further research are the development of medicinal and cosmetic products based on the hydrolates of the above-stated essential oil cultures.

System of antioxidant protection of young cattle under cadmium load

It is known that free radical oxidation of lipids is an essential stage in the influence of heavy metals on the animal body. That is why the work aimed to investigate the indicators of the antioxidant system in young cattle under conditions of cadmium loading. For research, 15 clinically healthy six-month-old bulls of the black and spotted breed were selected, from which 3 groups of five animals were formed. The animals in the control group were on a regular diet. The animals of the experimental groups with compound feed were fed cadmium chloride in doses of 0.03 and 0.05 mg/kg of body weight. Feeding young cattle with cadmium chloride feed caused a decrease in the activity of the enzyme system of antioxidant protection of their body. These changes are confirmed by a decrease in their blood activity of superoxide dismutase by 31 %, catalase by 13.4 %, glutathione peroxidase by 23.2 %, glutathione reductase by 22.2 %, and glucose-6-phosphate dehydrogenase by 32.4 %, respectively. A decrease in the level of indicators of the non-enzymatic link of the system of antioxidant protection of the body of young cattle under cadmium load was also established, where, accordingly, a decrease in the content of reduced glutathione was established – by 10.4 %, selenium – by 14.8 %, vitamin A – by 31.3%, of vitamin E – by 30.8% in their blood compared to the control. It is worth noting that on the sixteenth and twenty-fourth days of the experiment, the lowest value of the enzymatic and non-enzymatic links of the antioxidant protection systems of young cattle under conditions of cadmium loading was observed. In the future, a practical scheme for preventing cadmium toxicosis in young cattle by studying indicators of the antioxidant system is planned.

Modification of low-density lipoproteins by low molecular weight carbonyl products of free-radical oxidation of lipids and carbohydrates plays a key role in atherosclerotic lesion of the vascular wall and in endothelial dysfunction

The review presents evidence of the participation of low-density lipoproteins (LDL) modified by low molecular weight dicarbonyl compounds formed during freeradical oxidation of lipids (malondialdehyde) and carbohydrates in the development of endothelial dysfunction and atherosclerotic vascular lesions. The authors believe that it is they, and not oxidized (hydroperoxide-containing) LDL, that are the main factors of pathogenesis. The role of dicarbonyl-modified LDL in LOX-1 dependent induction of processes leading to the development of endothelial dysfunction is discussed. The results of studies proving that damage to the glycocalyx (a layer of macromolecules that prevent the development of endothelial dysfunction) covering the luminal surface of the endothelium is caused by hyperproduction of reactive oxygen species. Ways of pharmacological correction of free-radical oxidation processes are discussed, due to which inhibition of atherogenesis and diabetogenesis can be achieved.

THE INFLUENCE OF MELATONIN ON THE ACTIVITY OF THE MAIN ENZYMES OF ANTIOXIDANT PROTECTION IN THE HEART OF RATS WITH DEXAMETHASONE DIABETES

The goal of this study was to find out the influence of melatonin on the content of TBCreactive products; on the activity of the main antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the heart of rats with dexamethasone diabetes. Materials and Methods. The experimental study was carried out on thirty male eighteen-month-old non-linear white rats. The experimental animals were divided into three groups: 1) control (intact animals); 2) rats with diabetes; 3) rats to which, in addition to dexamethasone, melatonin in a dose of 10 mg per kg of body weight was administered intragastrically daily through a metal probe during the 13 days of experiment. Results. In the heart of rats with dexamethasone diabetes, the content of TBC-reactive products increases by 43% compared with control rats, which indicates an increase in the processes of free radical oxidation of lipids. At the same time, in the heart of diabetic rats, a decrease in the activity of the studied enzymes is noted: superoxide dismutase – by 28%, catalase – by 25%, and glutathione peroxidase – by 31%, respectively, compared with control rats. In the heart of rats, which, in addition to dexamethasone injections, received melatonin, the studied indicators did not differ reliably from the indicators of the control group of animals. Conclusions. The use of melatonin stopped the processes of free radical oxidation of lipids and restored the activity of the investigated enzymes of antioxidant protection in the heart of rats.

Oxygen-Dependent Blood Processes in Beck's Sarcoidosis

The objective: to assess the state of oxygen-dependent blood processes in patients with Beck's sarcoidosis.Subjects and Methods. Parameters of blood oxygen transport function and free radical lipid oxidation, as well as the content of nitrogen monoxide and hydrogen sulfide gas transmitters were assessed in the blood of 75 patients (41 women; 34 men) with Beck's sarcoidosis, stage 2 (the pulmonary mediastinal form).Results. In the pulmonary mediastinal form of sarcoidosis versus healthy individuals, there was a decrease in the degree of blood oxygen saturation from 65.4 (60.6; 67.8) to 41.50 (36.0; 49.8), p < 0.05, %, partial oxygen pressure from 40.0 (38.0; 47.0) to 23.0 (18.3; 29.0) mmHg, p < 0.05, and blood pH increased. A decrease in the index of hemoglobin affinity to oxygen p50real (26.80 (24.70; 31.40), p < 0.05, versus healthy individuals 28.2 (27.9; 29.1) mmHg) was revealed. The level of diene conjugates increased in plasma by 86.4% (p < 0.05) and malondialdehyde increased in erythrocytes by 139.2% (p < 0.05), while the following parameters decreased: α-tocopherol (by 42.7 %, p < 0.05), retinol (by 41.9%, p < 0.05), reduced glutathione (by 30.4%, p < 0.05), and ceruloplasmin (by 22.3%, p < 0.05) in plasma. There was an increase in the concentration of nitrogen monoxide (from 15.42 (14.48; 17.71) to 17.09 (7.04; 25.09), mmol/L) and a decrease in hydrogen sulfide (from 29.01 (25.21; 37.03) to 13.08 (8.63; 20.46), mmol/L) in the blood in case of this pathology.Conclusion. There is a deterioration in the blood oxygen-binding properties in patients with Beck's sarcoidosis, stage 2, and as a consequence, tissue needs in oxygen are not adequately provided by blood circulation. There is an increase in the concentration of nitrogen monoxide and a decrease in hydrogen sulfide, which affects the oxygen transport function of blood which may be important for ensuring the processes of oxygen transfer to tissues. In this pathology, activation of lipid peroxidation and a decrease in the level of antioxidant protection factors of blood were revealed which might be important for the genesis of this disease.

Регулирующие функциональные системы в патогенезе доброкачественной дисплазии молочных желез

This article presents an analysis of publications devoted to the role of functional systems in the development of benign breast conditions, which were selected from the scientific databases Russian State Library, elibrary, PubMed, Cochrane, Medline, Medscape. The results obtained indicate that the neuroendocrine, immune, and free radical lipid oxidation systems are involved in the development of benign breast pathology. Changes in these systems negatively affect a woman’s reproductive and breast health and increase the risk of breast cancer. Key words: hormones, benign breast pathology, immunity, free radical oxidation of lipids

Increasing the efficiency of hypolipidemic therapy with the combined use of quercetin in patients with non-alcoholic fatty liver disease on the background of the metabolic syndrome

The article analyzes the results of a set of biochemical indicators in the course of treatment with the combined use of rosuvastatin with quercetin in patients with metabolic syndrome (MS) combined with non-alcoholic fatty liver disease. Changes in blood biochemical parameters have been identified and presented with MS, essential for revealing generalbiological mechanisms development and interrelationship between the components of MS and non-alcoholic fatty liver. The effect of an increase in free cholesterol and triglycerides and activation of freeradical oxidation of lipids followed by theaccumulation of oxidative stress products was noted. In the course of long-term hypolipidemic therapy (90 days), 86 patients with non-alcoholic fatty liver disease on the background of metabolic syndrome were previously divided into 2 groups: a comparison group (45 patients), who weretreated with basic therapy – only rosuvastatin, the main group (41 patients) received quercetin together with rosuvastatin –40 mg 3 times a day, clinical and laboratory-instrumental examinations were carried out. On the 90th day of treatment, positive results in the functional state of the liver and lipid spectrum of the blood wereregistered in all patients. A more significant advantage of the therapeutic combination of rosuvastatin with quercetin was proved. The inclusion of quercetin contributed to reducing the intensity of oxidative stress and enhancing antioxidant protection activity, resultingin a decrease in apoptosis of hepatocytes (cytokeratin-18 level was 1.27 times decreased). The studies have shown the feasibility of combined use of quercetin with rosuvastatin for the prevention of the development and progression of metabolic disorders associated with non-alcoholic fatty liver disease.

SYNTHESIS AND PRECLINICAL STUDY OF ANTIOXIDANT ACTIVITY OF [1,2,4]TRIAZOLO[1,5-A]PYRIDINE DERIVATIVES

Purpose. Synthesis and study of antioxidant properties of [1,2,4]triazolo[1,5-a]pyridine derivatives and their potential toxicity using preclinical diagnostic methods. Methodology. Derivatives of [1,2,4]triazolo[1,5-a]pyridine were synthesized on the basis of 2-aminopyridines and ethyl isothiacyanatocarbonate, with subsequent cyclization of intermediate adducts. The resulting 2-amino[1,2,4]triazolo[1,5-a]pyridines were reacted with isoamyl nitrite in the presence of CuHal2, which led to the synthesis of volatile 2-halogeno[1,2,4]triazolo[1,5- a]pyridine. The toxicity of the obtained compounds was studied by the degree of hemolysis of erythrocytes in a hypotonic NaCl solution. The intensity of free-radical oxidation of lipids was assessed spectrophotometrically by the formation of TBА-active products. The antioxidant activity of the substances was determined by inhibiting the oxidation of adrenaline under conditions of artificial oxidative stress. Scientific novelty. For the first time, the antioxidant activity of the [1,2,4]triazolo[1,5-a]pyridine derivatives described in the paper was investigated and their toxicity was studied according to the degree of hemolysis of erythrocytes in a hypotonic NaCl solution. Conclusions. The in vitro cytotoxicity study model showed that compounds 5a and 5b, which contain bromine atoms in the 2, 5, and 7 positions of the pyridinotriazole heterosystem, exert the greatest influence on the stability of erythrocyte membranes. The study of antioxidant activity showed that the highest values of antioxidant activity are characteristic of compounds of the 4a-d series, namely compounds 4b and 4c, which are characterized by the presence of an amino group in the 2nd position and the presence of a bromine atom as a substitute in the 1st and 5th positions of the pyridine fragment of the heterosystem. The dynamics of antioxidant activity on the model of inhibition of adrenaline oxidation confirms the opinion about the lowest toxicity and the highest ability to inhibit the formation of reactive oxygen species of compounds 4b and 4c (40.16 and 38.82% relative to ionol). So, with the use of preclinical diagnostic methods, we proved the presence of physicochemical activity in a number of investigated compounds. 2-amino-[1,2,4]triazolo[1,5a]pyridine derivatives with a bromine atom as a substitute in the pyridine fragment of the molecule should be considered as potential antioxidants in the future, and the studied condensed system can be considered a promising heterocyclic framework for creating potential antioxidant agents.

Mitochondrial cerebral dysfunction in rats with scopolamine-induced neurodegeneration under enalapril effect

Objective. Neurodestructive diseases are characterized by complex pathobiochemical cascades in the neuron, which cause disturbances in energy metabolism and the formation of mitochondrial dysfunction. The renin-angiotensin system plays an important role in the physiological functioning of mitochondria, the excessive activity of which increases the risk of neurodegenerative diseases of the brain. Although angiotensin-converting enzyme inhibitors are now considered as means of prevention and treatment of ischemic lesions of the central nervous system, their corrective properties in the development of central neurodegeneration continue to be refined. The objective of our study was investigation of enalapril effect, as an angiotensin-converting enzyme inhibitor, in case of mitochondrial dysfunction of the cerebral cortex and hippocampus of rats under conditions of scopolamine-induced neurodegeneration reproducing development of Alzheimer’s disease in the experiment.Material and methods. Scopolamine hydrochloride (Sigma, USA) was injected in rats through the peritoneum at a dose of 1 mg/kg for 27 days to simulate Alzheimer’s disease. Starting from the 28th day of the experiment, enalapril was introduced through the peritoneum at a dose of 1 mg/kg, once a day for 14 days.
 Results. Under conditions of scopolamine-induced Alzheimer’s disease in the mitochondrial fraction of the cerebral cortex and hippocampus of rats free radical oxidation of lipids and proteins ncreases, and activity of Krebs cycle enzymes decreases – α-ketoglutarate dehydrogenase and succinate dehydrogenase; light dispersion decreases and a relative rate of mitochondrial swelling increases. After enalapril administration for 14 days to rats with scopolamine-induced Alzheimer’s disease the content of products reacting with 2-thiobarbituric acid and protein oxidation modification decreases in the mitochondrial fraction of the cerebral cortex and hippocampus; in both examined structures, the activity of catalase, αketoglutarate dehydrogenase, succinate dehydrogenase increases, and superoxide dismutase – only in the cerebral cortex; a gradual decrease of light dispersion and relative rate of mitochondrial swelling occurs.Conclusion. Improvement of the antioxidant system state and energy supply of mitochondria, decreased intensity of mitochondrial swelling in the cerebral cortex and hippocampus of rats with scopolamine-induced Alzheimer’s disease are indicative of the protective properties of enalapril.

Influence of impulse magnetic fields of extremely low frequencies on H2O2- and Fe2+-induced free radical lipid oxidation in liposomal suspensions

Background: For a long time, special attention in experimental biology and medicine is paid to free radical processes involving reactive oxygen species. In electromagnetic biology, the interest in free radical oxidation in biological membranes has increased significantly due to the discovery of spin mechanisms of magnetic fields on free radical processes. In the present day, these mechanisms are considered to be key in the processes of magnetoreception in living organisms. Liposomes, as the simplest models of biological membranes, are often used to study the primary mechanisms of action of different factors on the structural and functional properties of membranes. However, the influence of ecological significant extremely low-frequency magnetic fields on free radical oxidation in liposomal suspensions has not been studied enough. Objectives: The elucidation of the peculiarities of the influence of the extremely low frequency pulsed magnetic fields (ELF PMF) on H2O2- and Fe2+-induced peroxidation of natural phospholipids in liposomal suspensions. Materials and methods: The liposomal suspensions in phosphate buffer pH=7.4 were used. According to the literature and own results on light scattering the average diameter of liposomes was about 500Å. Ultra-weak chemiluminescence of liposomal suspensions was recorded using a device that operated in the mode of single photons counting. It consisted of a light-insulated cuvette unit where the test samples were placed, as well as a temperature sensor and a solenoid, which was used to create the PMF. Optical contact of the test samples with the photoelectron multiplier was carried out using a light guide. The recording system consisted of a broadband photomultiplier tube detector — FEU-130, which was at a temperature of –20°C. The pulse analyzer AI-256 was used to separate the useful signal that corresponded to the registration of single chemiluminescence light quanta. The voltage on the photomultiplier tube detector was applied in the range of current-voltage characteristics of this detector, in which a random voltage fluctuation had a minimal effect on the measurement of the useful signal. The number of light quanta that were recorded for defined time intervals characterized the overall intensity of the process of free radical oxidation of lipids in the experimental samples. The pulsed magnetic field was created using a solenoid coil located in the cuvette part. PMF was created using a serial generator G6-28. The magnetic field pulses were rectangular in shape with variable polarity for a period of oscillations. The induction of PMF was monitored using microteslameter G-79. The series of extremely low frequencies (5–80 Hz) and induction (5–500 μT) of PMF was chosen due to their environmental and physiological significance. Results: PMF of different frequencies with induction of 5 and 50 μT did not affect (p>0.05) H2O2- and Fe2+-induced lipid oxidation in liposomal suspensions. Statistically significant changes (p<0.05) were revealed only when liposomal suspensions were exposed to PMF with induction of 500 μT. It was found that the action of PMF with the frequency of 8 Hz 500 μT significantly inhibited H2O2-induced and enhanced Fe2+-induced chemiluminescence. This effect is associated with inhibition of the decomposition and with the accumulation of phospholipid hydroperoxides, which decompose and recombine in the presence of Fe2+ ions, which is accompanied by stronger chemiluminescence. The study of the dependence of the dynamics of the chemiluminescence intensity on the frequency of the PMF indicates the presence of a certain dependence of the effects in the range of up to 30 Hz. However, the inhibitory effect of PMF for the H2O2-induced oxidation phase is not always accompanied by a statistically significant increase in the amplitude of Fe2+-dependent light flash of chemiluminescence that indicates the general inhibitory effect of PMF at a certain frequency. Conclusions: PMF of extremely low frequencies statistically significantly affects the free radical oxidation in liposomal suspensions only at inductions exceeding several hundred microteslas. This indicates the effect of PMF on free radical processes for the conditions of the selected membrane model is realized mainly through spin interactions that determine the recombination of free radicals. The decrease of induction by one or two orders of magnitude, as well as increasing in frequency of the PMF above 50 Hz, leads to a decrease in the effectiveness of the influence of this physical factor on the intensity of lipid-free radical oxidation in liposomal suspensions. The most sensitive to the influence of ELF PMF is the phase of H2O2-induced free radical oxidation of lipids.

AGE PECULIARITIES OF PROOXIDANT-ANTIOXIDANT BALANCE OF THE ORAL FLUID IN PATIENTS AGAINST THE BACKGROUND OF INTAKT DENTITIONS, PARTIAL AND COMPLETE ANODONTIA

Relevance. The study is conditioned by a steady tendency of demographic aging of the population. On the part of the dental system, one of the most common age-related disorders is the tooth loss and the necessity to replace dentition defects. Changes in dental status can affect the course of oxidative reactions and antiradical protection of the oral fluid.
 Objective is to investigate the age peculiarities of the prooxidant-antioxidant balance of the oral fluid against the background of intact dentitions, partial and complete anodontia and their correction.
 Material and methods. There were examined 103 patients aged from 16 to 89, with intact dentitions, under the conditions of partial anodontia and correction with bridges or partial removable laminar dentures and complete anodontia and correction with complete removable laminar dentures. The intensity of the processes of free radical oxidation of lipids in oral fluid was assessed by the content of diene conjugates (DC) and products that respond to thiobarbituric acid (TBA-AP). The antioxidant reserve of the oral fluid was characterized according to the activity of superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR).
 Results. There was a significant increase of the indices of lipid peroxidation in the oral fluid, especially in middle-aged patients, which is confirmed by an increase in the content of DC and TBA-AP 5.9- and 4.5-fold, respectively, compared with data in adolescents. Such changes were consistent with a decrease in the activity of SOD, GP, GR of the oral fluid at 41.7-48.8% (p<0.05) relative to the values ​​in adolescence. In elderly and senile patients, the level of lipid peroxidation tended to decrease. The activity of antioxidant enzymes in elderly patients decreased at 28.6-49.8% (p<0.05), in the senile patients – at 29.6-63.6% (p<0.05) relative to the values ​​in the middle-aged patients. There has been an increase in the level of oxidative processes against the background of suppression of antiradical protection of the oral fluid in patients with partial or complete anodontia according to the data in the studied patients with intact dentitions, especially for people who use dentures.
 Conclusions. Prooxidant-antioxidant balance of the oral fluid depends on age and dental status. The most significant changes in oxidative processes in the oral fluid are observed in the middle-aged people with a tendency to decrease in the elderly and senile patients. The level of free radical processes increases under the conditions of partial and complete anodontia, correction of various types of denture designs and depends on the material they were made of. Such changes occur against the background of suppression of the antioxidant reserve of the oral fluid (especially the glutathione system).

Oxidative balance disorders as a factor of formation and progression of hypoandrogenism in boys

Objective — to study the features of the state of oxidative balance (processes of free radical oxidation and antioxidant protection) in boys with hypoandrogenism (HA). Materials and methods. Examinations involved 103 adolescent boys agreed 14 to 17 years with the delayed sexual development. Serum levels of total testosterone (TT), conjugated dienes (CD), thiobarbituric acid­reactive substance (TBARS), carbonylated proteins, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activity were determined. The coefficient of oxidative stress was calculated. Results and discussion. The following indicators have been revealed in patients with the delayed sexual development vs the comparison group: increased CD levels in 84.0 % of patients, elevated levels of carbonylated proteins in 53.7 % of adolescents, one third had raised TBARS levels; 63.0 % of patients demonstrated the increased GSH levels. Decreased activity of GPx and CAT was registered in more than half of the patients. Such changes indicate an imbalance in the ratio of free radical oxidation (FRO) and antioxidant protection, which leads to the state of OS in adolescents with delayed puberty.It was found that the redox balance in adolescents with delayed puberty significantly depends on the degree of androgen deficiency. Half of the patients with a degree I and II HA and 24.5 % of boys with degree III HA had elevated TBARS levels, which is more common in adolescents with normative values of TT. At the highest degree of androgen deficiency, the frequency of normative values of carbonylated proteins decreased. Most boys had elevated levels of CD (80 %), regardless of the degree of HA. An increase in SOD activity was found in patients with degree III HA. Low SOD activity was registered in 28.6 % of patients with degree II HA and 29.6 % with degree III HA, which is much less common compared to patients with normal TT levels. Most patients with HA, regardless of degree, were characterized by low GPx activity. Decreased CAT activity was registered in 76.9 % of patients with degree II HA. The majority of patients with HA (from 60.9 to 90 %) showed elevated levels of GSH, regardless of degree. The progression of HA in adolescents is characterized by the accumulation of products of free radical oxidation of lipids and an imbalance in the enzymatic and low molecular parts of the antioxidant system. This is typical for HA II and III degrees. The largest number of correlations was found in patients with degree III HA, testifying the formation of oxidative stress due to the activation of lipid peroxidation with simultaneous tension of the antioxidant defense system. Conclusions. The progression of HA is accompanied by the accumulation of products of free radical oxidation of lipids with simultaneous depletion of the enzymatic part of the antioxidant defense system. The activating effect of testosterone deficiency on the formation of oxidative stress in adolescents with the highest degree of androgen deficiency has been proven. This makes it possible to assess the state of oxidative balance as a factor in the formation and progression of HA in adolescents.

Pathogenetic Relationship of Immunological Disorders in Chronic Generalized Periodontitis and Rheumatoid Arthritis

The pathogenetic mechanisms of progression of chronic periodontitis accompanied with rheumatoid arthritis is confirmed by the common parts of immune-inflammatory reactions. Damage to periodontal tissues is indirectly made by cytotoxic effects of enzymes and their metabolites produced by Porphyromonas gingivalis bacteria. Neutrophils contribute to the progression of periodontitis and participate in its amplification by recruiting T-helper cells 17 and contributing to the accumulation of plasma cells in the affected tissues. Activation of immunocompetent cells promotes the generation of reactive oxygen species that initiate free radical oxidation of lipids, which, combined with the inability to neutralize them due to reduced antioxidant potential, leads to the development of oxidative stress. The connection between rheumatoid arthritis and chronic periodontitis has been the focus of numerous studies, due to their common pathogenetic mechanisms. Chronic inflammation associated with both rheumatoid arthritis and chronic periodontitis is similar in its prevailing adaptive immune phenotype, an imbalance between pro- and anti-inflammatory cytokines. The involvement of the Porphyromonas gingivalis microorganism in the generation of antibodies to citrullinated peptides in patients with rheumatoid arthritis is significant. The similarity of the epitope (SE) encoding the HLA-DRB1 allele, binding citrullinated peptides, can act as a basis for the approval of the genetic predisposition and mutual potential of these diseases. Thus, the proven connection between chronic periodontitis and rheumatoid polyarthropathies determines the significance of the analysis of the data obtained and substantiates the need for strategic research aimed at developing new methods in the diagnosis, treatment and prevention of the diseases for the purpose of breaking and separation of the common pathogenetic mechanisms of inflammatory reactions and osteoresorption processes leading to persistent functional and organic disorders.

Бенфотіамін як антиоксидант у дренажній зоні ока при поєднаному моделюванні глаукоми та діабету

During experimental glaucoma with diabetes in rabbits, in the filtering tissues of the eye, a state of oxidative stress is formed manifested by a significant decrease in the activity of antioxidant enzymes and the accumulation of products of free radical oxidation of lipids and proteins. Administration of a lipid-soluble form of vitamin B1 benfotiamine effectively reduced the manifestations of oxidative stress in the tissues of the anterior chamber of the animal eyes. This biologically active substance increased antioxidant capacity in tissues by activating antiradical protection enzymes: superoxide dismutase activity increased by 51%, catalase by 36% and glutathione peroxidase by 45% compared to the untreated animals. In addition, the processes of lipid peroxidation and oxidative destruction of protein molecules were decreased under the influence of benfotiamine. The level of malondialdehyde (MDA) was reduced by 47%, and the marker of oxidative damage to proteins of CO-groups by 35% relative to the untreated group. The results obtained may be a basis for further studies of the pharmacological substance benfotiamine in the clinic of glaucoma accompanied by diabetes, which will expand the arsenal of pathogenetically sound therapy of this serious disease.