[Influence of lactoferrin and enzymatiс hydrolysates of cow's and mare's milk proteins on anaphylactic sensitivity and cytokine profile of rats].

The development of innovative ingredients of specialized formula for children with intolerance to cow's milk proteins requires accounting the influence of the protein component on the allergic sensitivity. The aim of the research was to study the effect of lactoferrin (LF) from cow colostrum, cow's milk protein hydrolysate (CMPH) and mare's milk protein hydrolysate (MMPH) on the severity of the systemic anaphylaxis reaction, the levels of specific IgG antibodies and cytokines in rats parenterally sensitized with ovalbumin (OVA). Material and methods. The experiment was carried out on 4 groups of 26 male Wistar rats, which were sensitized intraperitoneally with chicken egg OVA and a systemic anaphylaxis reaction was induced on the day 29 by intravenous administration of a challenge dose of the antigen (6 mg per kg body weight). LF, CMPH and MMPH were introduced into the diet in doses of 1.4-2 g/kg body weight per day (on an average 1.59±0.04, 1.53±0.05 and 1.48±0.05 g per kg body weight respectively). The content of IgG antibodies in the blood serum was determined by an indirect ELISA; the levels of cytokines IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ and TNF-α were detected by multiplex immunoassay. Results. Dietary LF did not have a significant effect on the severity of active anaphylactic shock (AAS), concentrations of antibodies and cytokines in the blood of animals. As a result of CMPH consumption, there were no significant changes in AAS severity and IgG antibodies to OVA but significant increase in TNF-α level was observed as well as a significant decrease in IL-1α (p<0.05). In animals receiving MMPH, there were also no significant changes in the severity of AAS, but a 1.9-fold decrease in the level of IgG antibodies to OVA (p<0.001) was noticed along with a significant increase in IL-12(p70) (p<0.05) and IL-10 (p<0.10) level. Conclusion. Cosumption of LF by sensitized rats didn't significantly affect their anaphylactic sensitivity and cytokine profile, while CMPH intake induced some signs of pro-inflammatory processes. Consumption of MMPH was accompanied by the formation of an anti-inflammatory cytokine profile, which corresponds to a decrease in the intensity of the humoral immune response to the model allergen. Differences in the effects of two hydrolisates, which have similar degrees of hydrolysis, may be associated with the specific composition of glycopeptides formed during the enzymatic cleavage of milk protein produced by these two species of dairy animals.

[Multi-strain probiotic combined with dietary fiber is an effective factor in the nutritional support of immunity in athletes].

A priority in the prevention and correction of immune disorders in athletes is the use of products with high nutrient density, fortified with various nutrients or bioactive compounds, as well as probiotic microorganisms. Probiotics help to maintain the gut microbiota, which is actively involved in the absorption of substances and energy and increases the host immune resistance. Dietary fiber, resistant to digestion in the small intestine, is fully or partially fermented in the large intestine and acts as an essential substrate for the growth and regulation of metabolic activity of normal flora, improves peristalsis and digestion. The purpose of the study was to evaluate the impact of a multi-strain probiotic in combination with dietary fiber on the immune status of basketball athletes during the training period. Material and methods. The study was conducted with the participation of 30 male basketball athletes aged 18 to 24 years. The athletes were randomly divided into 2 groups of 15 people. Athletes in the main group received 1 capsule of multi-strain probiotic (≥1.25×1010 CFU of 10 probiotic strains of bifidobacteria and lactobacilli) and 40 g of corn bran (as a source of dietary fiber) for 23 days. Athletes in the control group received 1 placebo capsule containing maltodextrin and breadcrumbs (40 g/day). Subpopulations of peripheral blood lymphocytes were studied by flow cytometry: T lymphocytes, T helper cells, T cytotoxic lymphocytes, NK cells, NKT cells, B lymphocytes, as well as lymphocytes carrying activation markers and apoptosis marker antigen. The content of cytokines in blood serum [FGF, Eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ra, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, MCP-1, MIP-1α, MIP-1ß, PDGF-BB, RANTES, TNF-α, VEGF] was determined using a multiplex immunoassay. Results. Calculation of the absolute number of lymphocytes revealed a tendency (0.05

[Effect of microand nanoplastics as food contaminants on the immune system].

Currently, due to the increase in the distribution and accumulation of microplastics and nanoplastics (MP and NP) in the environment, their negative impact on human health has become a global problem. The purpose of this research was to analyze the results of the studies on the effect of MPs and NPs on the body and evaluate their impact as pathogenetic factors of immune status disorders in vitro and in vivo. Material and methods. The search for literary sources was carried out in the PubMed Internet resource, and the Scopus and Web of Science databases were also used. The Springer and Elsevier websites were used to access the full text of the articles. Results. MP and NP enter the human body through ingestion of food, water, as well as through inhalation and contact with the skin. The results of the studies indicate that MP and NP particles, entering the human body, can move along with the blood and accumulate in various organs: the liver, spleen, heart, lungs, thymus, reproductive organs, kidneys and brain, i.e., to overcome the blood-brain barrier. The immune system is the main regulatory and protective system of the body, playing a major role in the recognition and destruction of foreign antigens of a viral, bacterial and chemical nature. Innate immunity is the first line of defense against pathogens. Macrophages, monocytes, natural killer cells (NK cells), and leukocytes (neutrophils) phagocytize antigens and present them to adaptive immune cells. It has been established that the damaging effect of MPs and NPs on immunity (immunotoxicity) is mainly due to the presence of oxidative stress with the formation of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMP). The toxicity of MPs and NPs is realized by reducing the expression of the Nrf2 factor (a redox-sensitive transcription factor that regulates antioxidant protection) and the activation of p38 mitogen-activated protein kinases. In addition, it was found that the inflammatory process after exposure to MP and NPs is mediated by the expression of pro-inflammatory cytokines: IFN-γ, TNF-α, IL-1ß, IL-6 and IL-33 and a decrease in the expression of cytokines: IL-4, IL-5, IL-10, IL-33 and TGF-ß1, which leads to activation of the signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) and cGas/STING pathways. Conclusion. Analysis of the data of MP and NP effect on the immune system indicates the presence of aseptic chronic inflammation, which requires studying the causes and mechanisms of the development of inflammatory processes.

[Effect of L-carnitine and resveratrol complex on the profile of cytokines and regulatory proteins in normal and obese rats].

Chronic inflammation in adipose tissue, peripheral organs and some compartments of the brain are among pathogenetic factors in obesity. The use of bioactive compounds with anti-inflammatory and hypolipidemic activity in the composition of specialized products and dietary supplements is considered as an approach in the diet therapy of obesity and related conditions. The aim of the research was to study the effect of a complex supplement containing resveratrol and L-carnitine (RC supplement) on the immunological parameters of inflammation (the profile of cytokines and regulatory proteins) in rats fed a balanced or hypercaloric diet. Material and methods. Male Wistar rats received for 63 days a standard balanced diet (SD) or a high-carbohydrate-high-fat diet (HFCD) with an excess of total fat and fructose, as well as RC supplement at a low (25 mg/kg body weight as Res and 300 mg/kg body weight as L-Car) or high (50 and 600 mg/kg body weight, respectively) dose. The content of leptin, ghrelin, cytokines and chemokines in blood serum (BS), lysates of white adipose tissue (WAT) and spleen, amygdala and hippocampus of the brain, the content of regulatory proteins Akt, IRS-1, GCK-3a/b, p70/S6, BAD, m-TOR, PTEN and S6 ribosomal protein in the amygdala and hippocampus have been studied the by multiplex immunoassay. Results. In rats that consumed RC as part of SD, there was a decrease in the levels of leptin and its ratio with ghrelin, the levels of proinflammatory cytokines (TNF-α, IL-1α, IL-12p40 and IL-12p70, IFN-γ) in BS and WAT, chemokines (MCP-1, M-CSF, MIP-2) in WAT. Some of these effects were more pronounced at a low dose of RC than at a large dose, and some of them were also canceled or changed in direction in animals treated with HFCD. In the amygdala, RC consumption increased the content of both pro- and antiinflammatory cytokines; the most significant was the increase in IL-7 levels in animals fed SD, and RANTES in animals fed HFCD. In the hippocampus of rats, the RC intake had an insignificant effect on the levels of cytokines and chemokines. Akt-1 kinase and the substrate of the insulin receptor IRS-1 were the main targets of RC action in the regions of the brain. Conclusion. The complex dietary supplement RC exerted a hypoleptinemic effect, revealed certain anti-inflammatory effects and modulated a number of the brain factors influencing behavioral responses in obesity. However, the synergistic effect of resveratrol and L-carnitine in the composition of the supplement wasn't not observed, and the effectiveness of its action decreased in conditions of a hypercaloric diet consumption.

[Assessment of the influence of an enzymal preparation - a complex of glucoamylase and xylanase from Aspergillus awamori Xyl T-15 on the intestinal microbiom and immunological indicators of rats].

The requirements for the safety of food products obtained by microbial synthesis are including as obligation for to conduct toxicological studies - the study of various biochemical and immunological markers of toxic effects. The necessity of these studies is explained by a possible change in the structure of food ingredients produced by a microbial cell and, consequently, a change in their biological properties, as well as the possible presence of living forms and/or DNA of producer strains or of their toxic metabolites in these ingredients. At the same time, it is well known that the nutrient composition of foods has a significant impact on the composition and properties of microorganisms that make up the gut microbiome, which, in turn, determines the immune status. The purpose of the research was to justify the analyses of gut microbiocenosis composition for inclusion in the protocol of safety investigation of foods obtained by microbial synthesis [on the example of an enzyme preparation (EP) - a complex of glucoamylase and xylanase from a genetically modified strain of Aspergillus awamori Xyl T-15]. Material and methods. In experimental studies carried out for 80 days, Wistar rats (males and females) were used. The study of the effect of EP (a complex of glucoamylase and xylanase from a genetically modified Aspergillus awamori Xyl T-15 strain) in dozes 10, 100 and 1000 mg/kg body mass on the cecum microbiome and the immune status (content of cytokines and chemokines: IL-1a, IL-4, IL-6, IL-10, IL-17A, INF-γ, TNF-α, MCP-1, MIP-1a and Regulated on Activation Normal T-cell Expressed and Secreted - RANTES) was carried out. Results. It has been shown that EP - a complex of glucoamylase and xylanase from A. awamori Xyl T-15 at doses of 100 mg/kg or more causes mild disturbances in the composition of gut microbiocenosis. At the same time, these disorders have a significant immunomodulat ory and immunotoxic effect on the body, which manifests itself in a dose-dependent change in the profile of pro-inflammatory cytokines and chemokines in blood and spleen. The adverse effect of EP on the body is probably due to the formation of metabolites that are not formed during usual digestive processes in the gastrointestinal tract. The minimum effective dose (LOAEL) of EP was 100 mg/kg body weight In accordance with established requirements, the activity of the EP should not appear in ready-to-use food. Subject to this requirement, amount of EP entering the body cannot exceed the established LOAEL level. Therefore, a complex of glucoamylase and xylanase can be used in food industry, subject to the establishment of regulations «for technological purposes¼ for A. awamori Xyl T-15 strain. Conclusion. The data obtained on the relationship between the state of the microbiome and the immune status upon the introduction of EP indicate the need to include indicators of the state of gut microbiocenosis in the test protocol of safety.

[Pathogenetic mechanisms for the development of hematological disorders in induced fatty liver disease in Wistar rats and assessment of the regulatory effects of carnosine and α-lipoic acid].

The study of the relationship between hematopoiesis and metabolism is now particularly relevant in view of the high incidence of alimentary dependent diseases, including non-alcoholic fatty liver disease. In this regard, pathogenetic factors of this disease development are studied actively in order to choose adequate drug therapy and usage of bioactive substances with antioxidant properties. The aim of the study was to study the pathogenetic relationship of hematological disorders and imbalance of growth factors, leptin and ghrelin in male Wistar rats in the model of the initial stage of non-alcoholic fatty liver disease development and to assess the regulatory effect of minor bioactive substances - carnosine and α-lipoic acid. Material and methods. The studies were performed on male Wistar rats with initial body weight 150±10 g within 8 weeks. Animals were divided into 5 groups (n=8 in each). Rats of the control group received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the combined addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. Hematological values were determined on a hematological analyzer. The content of ghrelin and leptin, as well as growth factors GM-CSF and M-CSF in blood plasma and adipose tissue lysates, was determined by multiplex immunoassay using xMAP technology. Results. Rat intake of HCCDD resulted in decreased hemoglobin levels and red blood cell scores compared to controls. Diet enrichment with carnosine and α-lipoic acid did not have a reliable effect on these indicators. Carnosine intake had a protective effect on erythrocyte volume, a decrease of which was recorded in other experimental groups. HCCDD stimulated the growth of the absolute number of leukocytes in peripheral blood due to granulocytes and mononuclears. The enrichment of HCCDD with carnosine and α-lipoic acid led to a further increase in leukocytosis, the maximum level of which was observed in the group of rats fed HCCDD, simultaneously enriched with carnosine and α-lipoic acid (14.86±1.48×109/l compared to 8.67±1.23×109/l in control). All diets used in the research had no effect on the number of erythrocytes and platelets in the peripheral blood of rats. The use of both HCCDD alone and in combination with carnosine or α-lipoic acid intake had a negative effect on the level of growth factors GM-CSF and M-CSF in blood plasma and adipose tissue. The consumption of HCCDD caused an increase in leptin blood level (8.54±0.69 compared to 2.58±0.37 pg/ml in control, р<0.05), which was normalized by enriching the diet with carnosine and α-lipoic acid. Ghrelin blood level significantly decreased in all experimental groups compared to the control: by 30% in rats fed and by almost 50% when carnosine and α-lipoic acid were added to HCCDD. The intake of α-lipoic acid led to hormone level changes in adipose tissue lysates, leptin content decreased (2.31±0.11 vs 2.77±0.15 pg/ml), while ghrelin level significantly increased (0.35±0.14 vs 0.20±0.06 pg/ml), compared with the control group (р<0.05). Conclusion. The revealed interrelation of parameters of the cellular composition of peripheral blood and hemoglobin content with the changes in the content of GM-CSF, M-CSF, leptin and ghrelin in blood plasma and adipose tissue indicates the mutual influence of the studied CSF, leptin, ghrelin and added antioxidants (carnosine and α-lipoic acid) on the regulatory mechanisms of hematopoiesis in rats fed HCCDD.

[Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats].

Non-alcoholic fatty liver disease (NAFLD) is now a common liver disease affecting about a third of the world's population. In this regard, the issue of studying the pathogenetic factors of the development of this disease in order to select adequate drug therapy and biologically active substances with antioxidant properties regulating the balance of pro- and anti-inflammatory cytokines is of particular relevance. The aim of the study was to assess the effect of minor biologically active substances - carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in the experimental model of the initial stage of NAFLD. Material and methods. The studies were performed on male Wistar rats with initial body weight of 150±10 g. Animals were divided into 5 groups of 8 rats each. Within 8 weeks, rats of the 1st group (control) received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. The study of rat hepatocyte apoptosis was performed by flow cytometry. Hepatocytes were stained with annexin V and vital dye 7-aminoactinomycin, followed by detection on an flow cytometer. The content of cytokines and chemokines (IL-1α, IL-10, IL-17А, M-CSF, MIP-1α, MIP-3α, RANTES) in the cytoplasmic fraction of liver tissue was determined by multiplex immunoassay. Results and discussion. On the model of the initial stage of development of NAFLD in male Wistar rats the еnrichment of HCCDD with carnosine and α-lipoic acid had demonstrated a protective effect on hepatocytes with a decrease in apoptosis intensity to the level in control rats. Under the influence of HCCDD, an increase in the content of M-CSF and MIP-1α and a decrease in the levels of MIP-3α and RANTES, stimulating the migration and differentiation of various immunoregulatory populations to the parenchyma at an early stage of the formation of fatty hepatosis, in the cytoplasmic fraction of liver tissue were detected. Moreover, a decrease in the level of proinflammatory cytokines IL-17A and IL-1α and an increase in IL-10 produced mainly by Treg-populations indicate the absence of pronounced inflammatory changes in the liver of male Wistar rats at the initial stages of development of fatty dystrophy. Conclusion. Enrichment of HCCDD with both carnosine and α-lipoic acid in Wistar rats had a protective effect on hepatocytes with a decrease in apoptosis to a level in control rats. The increase in the IL-10/IL-17A ratio indicates the activation of anti-inflammatory mechanisms due to the functional predominance of Treg-cells over Th1/Th17 lymphocytes.

Blood Cytokine Profile in Rats with Different Behavioral Characteristics after Metabolic Stress.

Changes in the blood cytokine profile in rats with various parameters of behavior were studied under conditions of 5-day starvation not followed by the recovery period or with subsequent normalization of food intake. Metabolic stress had no effect on the content of most cytokines. The concentration of pro- and anti-inflammatory cytokines in blood plasma of rats was shown to increase significantly by the end of a 5-day recovery period after food deprivation. These changes in behaviorally passive specimens were more pronounced than in active animals. Therefore, differences in the strain of immune reactions in mammals with different prognostic resistance to extreme factors are most pronounced during the post-stress period. These data illustrate the necessity of an individual approach to studying the systemic organization of physiological functions under normal and pathological conditions.

[Immunological markers of alimentary-induced hyperlipidemia in Wistar rats].

Changes in plasma levels of the main groups of cytokines and adipokines may correlate with the severity of metabolic disorders in hyperlipidemia and obesity. The aim of the study was to assess the significance of ghrelin, leptin, their ratio (L/Gh), and the cytokine profile as biomarkers at dietary-induced hyperlipidemia. Material and methods. We used 48 female Wistar rats with an initial body weight of 123±1 g, which were divided into 6 groups. Group 1 (control) received a balanced semi-synthetic diet according to AIN93; group 2 - diet with excess fat (30% by weight); group 3 - a diet with the addition of 20% fructose solution instead of drinking water, group 4 - a diet with excess fat and fructose, group 5 - a diet with added cholesterol (0.5%), group 6 - a diet with cholesterol and fructose. On the 64th day of the experiment, the mass of internal organs was determined; the levels of cytokines and adipokines in blood plasma were measured by multiplex immunoassay. Results and discussion. A decrease in the level of leptin was found in group 5 compared with the control and with groups 2, 4 and 6 groups (p<0.05). The lowest level of ghrelin was found in group 2 (p<0.05) against the background of high concentrations of leptin. Significant correlations were found between L/Gh and the total mass of animals (r=0.321; р=0.034), the relative mass of adipose tissue (r=0.439; р=0.003) and with the relative mass of the spleen (r=-0.460; р=0.003). In group 2, at the maximum L/Gh ratio, a significantly higher weight of adipose tissue was found, whereas in groups 3 and 5, at the lowest L/Gh ratio, the relative amount of total fat was the lowest. L/Gh ratio correlated with the level of monocyte chemotactic protein-1 (MCP-1), RANTES, IL-18 and macrophage colony-stimulating factor (M-CSF). The concentrations of IL-17, IL-18, IL-4, IL-5, MIP-3a, IFN-γ, M-CSF and RANTES in the experimental groups were reduced compared with the control, with the most pronounced effect in group 5 together with the lowest L/Gh ratio. Conclusion. The presence of a significant correlation between L/Gh ratio and changes in the weight of rats' body, spleen, adipose tissue, as well as levels of cytokines involved in inflammation regulation, confirms the importance of L/Gh ratio as a biomarker in an in vivo model of dyslipidemia.

[Immunomodulating effects of using L-carnitine and coenzyme Q10 in the nutrition of junior athletes].

Nowdays, much attention is paid to the study of disorders of immune regulation and methods of effective immune correction in athletes. In this regard, the use of specialized sport foods (SSF), containing nutrients with immunomodulatory properties, is of particular relevance in youth sports. The aim of the work is to study the immunomodulating activity of L-carnitine and coenzyme Q10 in junior athletes during the training period. Material and methods. The object of the study were 30 junior athletes (masters of sports and candidates for masters of sports in swimming) aged 14-18 years, including 9 girls and 21 boys. Athletes were divided into 3 groups of 10 people each. Athletes of the 1st and 2nd main groups received L-carnitine (600 mg per day) and coenzyme Q10 (60 mg/day), respectively, for 4 weeks in addition to the basic diet. The dosage of SSF used in the study was 200% of the adequate level of consumption and did not exceed the upper permissible level of consumption. Athletes of the 3rd group (control) received only basic diet without sports' nutrition. Examination of athletes of all groups was performed at the beginning and after 4 weeks of the observation period. Results and discussion. As a result of a comprehensive survey of junior athletes, the positive effect of L-carnitine intake on erythrocyte hemoglobin content (30.2±0.4 vs 28.3±0.3 pg at the beginning) was observed. The relative content of basophilic leukocytes in athletes of the main groups statistically significantly decreased by the end of the observation period: in the L-carnitine group, from 0.64±0.05 to 0.45±0.04%, in the coenzyme Q10 group, from 0.66±0.07 to 0.50±0.04%, which indicated an increase in the body's resistance to allergic reactions. Conclusion. The biomarkers of the immunotropic effect of L-carnitine and coenzyme Q10 are a decrease in the expression of the apoptotic marker CD95/Fas on peripheral blood lymphocytes and suppression of the production of pro-inflammatory cytokines synthesized by Th1-lymphocytes with switching the response to humoral immunity. An evidence base for the effectiveness of the use of L-carnitine and coenzyme Q10 in sports nutrition for restoring immune dysfunction and adaptive potential of junior athletes has been provided.

[The efficiency of branched chain aminoacids (BCAA) in the nutrition of combat sport athletes].

Balanced nutrition of athletes involves the usage of both ordinary products and complexes of functional food ingredients that contribute to improving the performance of athletes, strengthening the immune system. One of the main components of specialized foods that are widely used in sports' nutrition and food supplements are branched chain aminoacids (BCAA): valine, leucine, isoleucine. The aim of the work was to study the effect of the BCAA intake on the parameters of body composition and the immune status of combat sport athletes during the training period. Material and methods. The object of the study was 20 athletes (masters of sports and candidates for masters of sports in combat sports: sambo, judo) at the age of 17-18 years. Athletes were distributed into 2 groups. Athletes of the main group (n=10) for 4 weeks in addition to the main diet were supplemented with BCAA at a dosage of 5 g per day. The athletes of the control group (n=10) received the main diet without BCAA inclusion. Examination of athletes of both groups was carried out at the beginning of the research and after 4 weeks of the observation period. The actual nutrition of athletes and daily energy consumption have been studied, body composition, the quantitative composition of subpopulations of peripheral blood lymphocytes, cytokine profile and hematological parameters have been determined. Results and discussion. As a result of a comprehensive survey of athletes, the positive effect of BCAA intake on the phase angle value (7.35±0.28 vs 6.41±0.32 at the beginning of the study, p<0.05) and muscle mass (25.1±0.8 vs 23.4±0.6 kg, p<0.10) has been demonstrated. In the control group these parameters did not change statistically significantly (7.05±0.25 vs 6.78±0.42 and 24.1±1.7 vs 23.8±1.5 kg). The athletes of the main group showed an increase in erythrocyte hemoglobin content (30.0±0.3 vs 29.0±0.2 pg, p<0.05). The relative content of basophilic leukocytes in athletes of the main group decreased by the end of the observation period - from 0.69±0.05 to 0.54±0.05% (p<0.05), that indicated an increase of immune resistance. The biomarker of the immunotropic effect of BCAA was the suppression of IL-4 production (1.6±0.1 to 1.3±0.1 pg/ml, p<0.05) synthesized by Th2 lymphocytes, with switching response to cellular immunity. Conclusion. The results of this study provide evidence of the effectiveness of BCAA usage in sports' nutrition for maintaining sport performance, immunity, and the adaptive potential of combat sport athletes.

[Effect of B-vitamin deficiency on biochemical, immunologic markers and trace element status of rats and mice of various lines].

Biochemical, vitamin, trace element and immunological changes were searched for the combined nutritional deficiency of vitamins B1, B2, B6 on in vivo models in rats and mice. Female rats of Wistar (W) strain and hybrids of the 1st generation of Dark Aguti and Wistar (DA x W) strains, female mice of BALB/c strain and DBCB tetrahybrids were used in experiment. Animals received for 35 days a balanced diet (control) according to AIN-93 or a similar diet with the exception of vitamins B1, B2, B6 (experimental groups). The content of vitamins B1, B2 in liver, riboflavin blood plasma level and urinary excretion of thiamine, riboflavin and 4-pyridoxic acid were determined, as well as in rats: blood and liver content of α-tocopherol and retinol, blood biochemical indices of lipid and nitrogen metabolism, activity of cytochrome P isoforms-450 (CYP) in liver; in mice: the circulating levels of pro- and anti-inflammatory cytokines of blood plasma, in animals of both species - the content of essential and toxic elements in the kidneys. DAxW rats compared to W and DBCB mice compared to BALB/c were more sensitive to the development of B-vitamin deficiency judging by the B-vitamin status indicators. In the rats of the experimental groups, there were signs of a deterioration in blood and liver levels of vitamin E, multidirectional shifts in vitamin A sufficiency, increased activity of the CYP3A isoform (6ß-TG), a decrease in triglycerides, total protein and albumin fraction levels with an increase in urea level. Manifestation degree of these effects depended on the choice of the animal's line. In mice, the B-vitamin deficiency was characterized by an increase in the levels of proinflammatory cytokines TNF-α, IL-10, IL-Ιß, IL-6 and a decrease in IFN-γ and IL-17A. The content of magnesium, copper, zinc, chromium and silver was lowered, of cesium - was increased in the kidneys of the rats of the experimental groups. In mice, B-vitamin deficiency resulted in diminishment of magnesium, copper, zinc, chromium, selenium, cadmium and lead content, excess accumulation of cobalt and cesium. Some of these biomarkers are supposed to be used in pre-clinical evaluation of the effectiveness of new vitamin complexes, specialized foods and dietary supplements, as well as studies of interactions of various vitamins.

[Characteristic of the rats' immune status during vitamin and mineral deficiency].

The article presents the results of rats' immune status evaluation in conditions of different levels of B vitamins (B1, B2, B3, B6) and minerals (Fe3+ and Mg2+) supplying. Male Wistar rats (with initial body weight 90-110 g) within 65 days received model diets with 75, 30 and 19% content of the essential substances, females (with initial body weight 56-76 g) received diets with 75, 28 and 18% content. Some indicators of humoral and cellular immunity, including leukocyte count, lysozyme serum activity, IgG and IgE level, cytokine profile of blood serum and of the masses of the immune system internal organs have been examined. It has been shown that the decrease in the content of B vitamins, iron and magnesium in the diet didn't cause complex changes of the rats' immune status, therefore, the proposed model of adaptive potential change is not optimal for studying of immune system condtion. The extensive research of the immune status of rats (18 studied indicators, a sample of 90 males and 90 females) allows to set the range of physiological fluctuations of these indexes in Wistar rats of the corresponding gender and age.

[Carbon nanotubes: mechanisms of the action, biological markers and evaluation of the (review of literature)].

The article contains the review and analysis of data on the mechanisms of the toxic action of carbon nanotubes (CNTs) on the body and available results of CNT toxicological evaluation after inhalation and oral routes of the action. Identification of cellular and molecular mechanisms of CNTs toxicity allows to justify the list of the most sensitive biochemical toxicity markers that could be used for monitoring the occupational effects of CNTs and serve as a promising target for the corresponding pharmacological and immunopharmacological interventions aimed on specific prophylaxis and therapy of diseases caused by CNT. A considerable amount of experimental data obtained in vivo on inhalation animal models allows to establish the hygienic standardfor CNT in the air of the working area. As to safe levels of the oral route of CNT it needs further study for their reliable assessment. The search and selection of sources for the review was executed with the use of public databases, including (in order of relevance) PubMed, Scopus, Google Scholar, and RISC, for the period from 2004 to 2017.

Evaluation In Vitro of Immunoregulatory Cytokines Secretion by Dendritic Cells in Mountain Skiers.

In vitro production of immunoregulatory cytokines (IFN-α, IL-31, TNF-ß, IL-17A, IL-7, IL-1RA, IL-1α, IL-10, IL-15, IL-21, IL-22, IL-23, IL-27, and IL-9) by dendritic cell cultures was compared in ski athletes and healthy donors. Effect of prolonged intense physical exercise on secretory activity of immune cells was investigated. In both groups, secretion of IL-1RA, IL-10, IL-1α by dendritic cells was revealed, but there were significant differences in IL-1RA, IL-1α content (p<0.05) with lower level in the group of athletes. Production of IL-17A and IL-7 by dendritic cells in the group of athletes was not detected. In athletes, several proinflammatory cytokines (IFN-α, IL-31, and TNF-ß) were secreted by cells in high concentrations, in contrast to the control group. In both groups, dendritic cells did not secrete IL-15, IL-21, IL-22, IL-23, IL-27, and IL-9.

[Comparative characteristics of in vivo models of hyperlipidemia in Wistar rats and C57Bl/6 mice].

In vivo simulation of lipid disorders (hyperlipidemia, obesity, metabolic syndrome, atherosclerosis) is of considerable interest to search for genomic, transcriptomic and metabolomic markers that allow for differential diagnosis, prognosis and selection of personalized diet therapy in patients with such pathology. The aim of the study was the development and characterization of basic biochemical parameters of in vivo models of alimentary hyperlipidemia in outbred rats and inbred mice. The experiment was con­ducted on 48 growing female Wistar rats, and 48 growing female mice of line C57Black/6, which were divided into 12 groups of 8 animals per group. Within 63 days the rats and mice of first (control) group received a balanced semi synthetic diet (BD), the animals of the second groups - high-fat diet (HFD) with 30% of the total fat by weight of dry feed, third groups - BD and fructose solution (Fr) instead of water, the fourth groups -HFD + Fr, fifth groups - BD supplemented with 0.5% cholesterol (Cho) by weight of dry feed, sixth groups - BD with Cho and Fr. The amount and composition of diets consumed were corrected during the experiment for their closest approach in calories. After removal of animals from the experiment there were determined the mass of internal organs, HDL, LDL, total cholesterol, triglycerides, glucose in blood plasma, total lipids and their fatty acid composition in liver, ghrelin, GIP, GLP-1, glucagon, leptin, PAI-1, resistin levels in blood plasma. It was found that in both species the liver is the most sensitive to nutritional imbalance, nutrient exerting the greatest impact on this was Fr. In rats, as compared to mice, there was significantly more pronounced shifts in lipoprotein spectrum in response to nutritional imbalances, especially to the consumption of additional Cho, which was manifested in an increase of LDL, decrease of HDL and magnification of atherogenic index. In the liver of rats fed diets with Cho, marked steatosis developed manifested in a disproportionate increase in the lipid content and accompanied by changes in their fatty acid composition, especially in the ratio ω6 to ω3 PUFAs. Changing of hormones - regula­tors of carbohydrate metabolism (GLP, glucagon) and ghrelin was significantly greater in mice than in rats as a result of consumption of additional Fr. Effect had the opposite direction in two species of Cho and Fr combining on leptin levels. The significance is dis­cussed of the revealed interspecies differences in the light of the characteristics of lipid and glucose metabolism in these two lines of animals that are the most common models of alimentary-dependent diseases.

[Effect of minor bioactive food substances ­ rutin and hesperidin in their separate and combined alimentary arrives on the immune system of rats and the activity of nuclear factor NF-kB liver cells].

The effect of rutin and hesperidin in their separate and combined admission to the immune system and the activity of nuclear factor NF-kB of rat liver cells has been investigated. Wistar male rats with an initial body weight of 224­225 g were divided into 4 groups of 6 rats in each. The rats of the 1st group (control) received a complete semi-synthetic diet, rats in group 2 ­ the same diet supplemented with rutine (400 mg/kg b.w.); the rats of group 3 ­ with the addition of hesperidin (400 mg/kg bw); group 4 ­ with the addition of rutin and hesperidin (400 mg/kg b.w. each) for 14 days. Animals received feed in free access mode in an amount of 25­30 g per rat per day, that corresponded to 15 g of dry formula. Animals received water also in free access. It has been found that rutin and hesperidin, included in the diet of rats both alone (groups 2 and 3) and together (group 4), have immunomodulatory impact which is a reduce of lymphocyte relative content [1st gr. ­ 70.55±1.58%, 2nd gr. ­ 63.62±2.85%, 3rd gr. ­ 62.03±3.16% (p1­3<0.05), 4th gr. ­ 65.75±1.08% (p1­4<0.05)] and an increase of percentage of neutrophil leukocytes [1st gr ­ 19.98±0.97%, 2nd gr. ­ 25.35±3.14%, 3rd gr. ­ 28.27±3.30% (p1­3<0.05), 4th gr. ­ 24.15±1.52% (p1­4<0.05)] and NK-cells in the peripheral blood [1st gr. ­ 3.29±0.45%, 2nd gr. ­ 6.91±0.70% (p1­2<0.05), 3rd gr. ­ 5.88±0.79% (p1­3<0.05), 4th gr. ­ 4.64±0.32% (p1­4<0.05)], that can be considered as a shift in the direction of innate immunity factors. In addition, the combined effect of high doses of rutin and hesperidin led to a change in erythrocyte parameters: an increase in the average volume of red blood cells [1st gr. ­ 56.00±1.06 fl, 2nd gr. ­ 56.67±0.42 fl, 3rd gr. ­ 58.50± 0.99 fl, 4th gr. ­ 59.50±0.99 fl (p1­4<0.05)], and the average content of hemoglobin [1st gr. ­ 18.97±0.45 pg, 2nd gr. ­ 19.10±0.19 pg, 3rd gr. ­ 19.73± 0.32 pg, 4th gr. ­ 20.08±0.33 pg (p1­4=0.07)], as well as increase in the level of TGF-ß1 in peripheral blood [1st gr. ­ 15.55±2.13 ng/ml, 2nd gr. ­ 14.81± 2.36 ng/ml, 3rd gr. ­ 17.02±2.53 ng/ml, 4th gr. ­ 22.14±2.29 ng/ml (p1­4<0.05)] and the expression of nuclear factor NF-kB in the liver cells [1st gr. ­ 16.10± 0.60 ng/ml; 2nd gr. ­ 15.14±2.28 ng/ml; 3rd gr. ­ 15.85±2.09 ng/ml; 4th gr. ­ 20.49±1.68 ng/ml (p1­4<0.05)].

[Study of the neuroprotective effects of carnosine in an experimental model of focal cerebral ischemia/reperfusion]. / Issledovanie neiroprotektornykh mekhanizmov deistviia karnozina pri éksperimental'noi fokal'noi ishemii/reperfuzii.

Oxidative stress is one of the key factors in brain tissue damage in ischemia, which indicates the appropriateness of using antioxidants under these conditions. One of the promising antioxidants for the therapy of ischemic stroke is the natural dipeptide carnosine. The neuroprotective effect of dietary carnosine administration was investigated in an experimental model of focal cerebral ischemia/reperfusion in Wistar rats. Animals received carnosine with a diet at a daily dose of 150 mg/kg for 7 days before temporary occlusion of the middle cerebral artery (MCA), performed for 60 min. At 24 h after the onset of ischemia the effect of carnosine on the area of the necrotic core was evaluated in animals. In brain tissue of animals the content of malondialdehyde (MDA), protein carbonyls (PC), total antioxidant capacity (TAC), total activity of superoxide dismutase (SOD), glutathione peroxidase (GP), catalase (CAT) and glutathione transferase (GT), content of isoprostanes and cytokines were measured. Carnosine significantly reduced the infarct size. Carnosine also increased TAC and reduced the level of MDA and isoprostanes in brain tissue. Influence of carnosine on other parameters was not detected. Thus carnosine consumed prophylactically with the diet for 7 days before the induction of ischemia by means of MCA occlusion in rats provides the direct neuroprotective effect, retains high antioxidant activity of brain tissue, reduces the level of oxidative damage markers (MDA and isoprostanes) but does not have any effect on the activity of antioxidant enzyme systems and production of cytokines in brain tissue.