Bacterial nanocellulose (BNC) is being considered as a potential replacement for microcrystalline cellulose as a food additive and a source of dietary fiber due to its unique properties. However, studies on the risks of consuming BNC in food are limited, and it is not yet approved for use in food in the US, EU, and Russia. Aim: This study aims to perform a toxicological and hygienic assessment of the safety of BNC in a subacute 8-week administration in rats. Methods: BNC was administered to male Wistar rats in doses of 0, 1.0, 10.0, and 100 mg/kg body weight for 8 weeks. Various parameters such as anxiety levels, cognitive function, organ masses, blood serum and liver biochemistry, oxidative stress markers, vitamin levels, antioxidant gene expression, and liver and kidney histology were evaluated. Results: Low and medium doses of BNC increased anxiety levels and liver glutathione, while high doses led to elevated LDL cholesterol, creatinine, and uric acid levels. Liver tissue showed signs of degeneration at high doses. BNC did not significantly affect vitamin levels. Conclusion: The adverse effects of BNC are either not dose-dependent or fall within normal physiological ranges. Any effects on rats are likely due to micronutrient deficiencies or impacts on intestinal microbiota.

Despite the widespread use of oat β-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. The purpose of the study was to evaluate the effect of including oat bran with a high content of β-glucans (β-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of β-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with β-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. Results. Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of β-glucans in the diet. At the same time, against the background of the presence of β-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with β-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. Conclusion. The presence of β-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.

Despite the use of yeast β-glucans in food and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and mineral elements. The aim of the study was to evaluate the effect of β-glucans from Saccharomyces cerevisiae in the diet of growing rats on the absorption of micronutrients in animals deficient in vitamins D, group B and trace elements (iron, copper, zinc). Material and methods. Micronutrient deficiency in male Wistar rats (initial body weight 61.6±0.8 g) was induced for 24 days by decreasing the content of vitamin D and all B vitamins in the vitamin mixture of the semi-synthetic diet by 5 times and the content of iron, copper and zinc in the mineral mixture by 2 times. After confirming the development of micronutrient deficiency in the animals, the missing vitamins and trace elements were added to the deficient diet for 5 days either along with β-glucan diet enrichment (1.5%) (+Vit+Met+βG) or without it addition (+Vit+Met). Vitamins B1 and B2 in the liver, riboflavin in the blood serum, thiamine, riboflavin and 4-pyridoxic acid (4-PA) in the urine collected for 18 hours were determined fluorimetrically; retinol, retinol palmitate, α-tocopherol in blood serum and liver - by high-performance liquid chromatography; minerals and trace elements in liver, serum and urine - by atomic absorption spectrometry or by standard methods on a biochemical analyzer. Results. A deficient diet for 24 days resulted in a decrease of B-vitamin status markers: riboflavin decreased in urine by 17.8- fold, in serum by 27.3% and in liver by 7.8%, vitamin B1 in liver by 3-fold, 4-PA in urine reduced by 2.8-fold (p<0.05). Urinary excretion of copper diminished by 25.7%, while the liver content of vitamin A increased by 44% and manganese by 19.2% (p<0.05). Replenishment of missing micronutrients in the diet, regardless of β-glucans presence, completely eliminated the deficiency of vitamin B2, while in the presence of the polysaccharide, rats of the +Vit+Met+βG group showed a statistically significant increase in vitamin B2 liver content by 7.5% (p<0.05) relative to the control, with an increased excretion of riboflavin by 19.1% (p<0.10) compared to excretion in +Vit+Met rats. Vitamin B1 liver level in animals of +Vit+Met and +Vit+Met+βG groups didn't completely restore to the control level but it was higher by 14.5% (p<0.05) in the presence of β-glucans. Urinary excretion of thiamine and 4-PA in rats fed β-glucan enriched diet reached the level of the control rats, while in rats from +Vit+Met group it amounted to 60.8-69.2% of the control. The diet with β-glucans caused a decrease in vitamin E liver content by 36.2% (p<0.05) compared to the level in +Vit+Met animals. Urinary excretion of iron and copper in the absence of β-glucans did not fully recover (amounting to 60.9-74.0% of the control), while in their presence it no longer differed from the value in animals of the control group. Zinc excretion in animals of the +Vit+Met+βG group, on the contrary, was lower than in the control by 29.2% (p<0.01). A decrease in serum magnesium (by 9.0%, p<0.05) with simultaneous increase (by 12.7%, p<0.10) in its urinary excretion under β-glucans' diet inclusion indicate a decrease in its retention and a deterioration in magnesium supply. Conclusion. The presence of yeast β-glucans in the diet improved the absorption of B vitamins, promoted the absorption of iron and copper, but worsened the supply with vitamin E and magnesium, and reduced zinc assimilation.

Liver morphology, intensity of apoptosis, and activity of xenobiotic metabolism enzymes were studied in a chronic model experiment in rats receiving a mixture of 6 pesticides against the background of life-long diets with adequate and insufficient supply of water-soluble vitamins. The dose of each pesticide in the mixture did not exceed the acceptable daily intake (1 ADI). It was found that chronic exposure to low doses of anthropogenic toxicants in combination with permanent vitamin deficiency provokes a number of liver changes, such as increased apoptosis activity, cytochrome P450 system depletion, steatosis, and inflammatory infiltration, which is a potential health risk factor.

The choice of an optimal biological model of exogenous hypercholesterolemia is necessary for correct assessment of the cholesterol-lowering properties of bioactive substances and specialized food products and for validity of the experimental results. We studied the effects of cholesterol consumption in the composition of the standard semi-synthetic diet and high-fat high-carbohydrate diet for more than 3 months on lipid and cholesterol metabolism in male Wistar rats. Our findings suggest that cholesterol consumption in both diets led to a significant impairment of lipid and cholesterol metabolism, as well as an increase in insulin resistance in rats.

Dihydroquercetin (3,5,7,3',4'-pentahydroxy-flavanone) is known for its powerful antioxidant, organ-protective, and antiinflammatory activities that can be applied to heavy-metal intoxication. The present research objective was to evaluate the possible protective potential of dietary dihydroquercetin in a rat model of subacute (92 days) intoxication with nickel nanoparticles. The experiment involved five groups of twelve male Wistar rats in each. Group 1 served as control. Other groups received nickel nanoparticles as part of their diet. Groups 2 and 4 received nickel nanoparticles with an average diameter of 53.7 nm (NiNP1), while groups 3 and 5 were fed with nanoparticles with an average diameter of 70.9 nm (NiNP2). The dose was calculated as 10 mg/kg b.w. Groups 4 and 5 also received 23 mg/kg b.w. of water-soluble stabilized dihydroquercetin with drinking water. After the dihydroquercetin treatment, the group that consumed 53.7 nm nickel nanoparticles demonstrated lower blood serum glucose, triglycerides, low-density lipoprotein cholesterol, and creatinine. Dihydroquercetin prevented the increase in total protein and albumin fraction associated with nickel nanoparticles intake. The experimental rats also demonstrated lower levels of pro-inflammatory cytokines IL-1β, IL-4, IL-6, and IL-17A, as well as a lower relative spleen weight after the treatment. In the group exposed to 53.7 nm nickel nanoparticles, the dihydroquercetin treatment increased the ratio of cytokines IL-10/IL-17A and decreased the level of circulating FABP2 protein, which is a biomarker of increased intestinal barrier permeability. In the group that received 70.9 nm nickel nanoparticles, the dihydroquercetin treatment inhibited the expression of the fibrogenic Timp3 gene in the liver. In the group that received 53.7 nm nickel nanoparticles, dihydroquercetin partially improved the violated morphology indexes in liver and kidney tissue. However, dihydroquercetin restored neither the content of reduced glutathione in the liver nor the indicators of selenium safety, which were suppressed under the effect of nickel nanoparticles. Moreover, the treatment failed to restore the low locomotor activity in the elevated plus maze test. Dihydroquercetin treatment showed some signs of detoxication and anti-inflammation in rats subjected to nickel nanoparticles. However, additional preclinical studies are necessary to substantiate its prophylactic potential in cases of exposure to nanoparticles of nickel and other heavy metals.

The lack of vitamins D, B group, calcium and magnesium is common for the diet of the Russian population. It has been previously demonstrated that that the elimination of B vitamin deficiency is a necessary condition for the implementation of vitamin D biological functions. The aim of the research was to assess the effect of a combined deficiency of vitamins D and B group, calcium and magnesium in the diet of rats on biomarkers of micronutrient sufficiency and plasma biochemical indicators. Material amd methods. Male Wistar rats with an initial body weight of 66±1 g were randomly assigned to one of five groups. The rats of the 1st group (Control) were fed a standard semi-synthetic diet (SD) for 28 days. The combined deficit of vitamins D and B group, calcium and magnesium in rats of four experimental groups was caused by a 5-fold decrease in their content in the vitamin mixture and 2-fold decrease in their content in mineral mixture of the SD for 23 days. Over the next 5 days, the rats of 2nd group (+В+D+Ca+Mg) were fed a diet replenished for all missing vitamins and minerals, the rats of 3rd group (-В+D+Ca+Mg) were fed a diet with continued deficiency of B group vitamins, the rats of the 4th group (+В+D-Ca-Mg) were fed a diet with continued lack of calcium and magnesium, the diet of the 5th group (-B-D-Ca-Mg) was not replenished. Vitamins B1 and B2 in lyophilized liver and brain and urine, riboflavin in plasma and 4-pyridoxic acid in urine were determined by fluorimetric methods, 25(OH)D in plasma was determined by ELISA, the level of vitamins A and E in blood plasma and lyophilized liver, of vitamin E in whole brain - by HPLC. Biochemical parameters of blood plasma were determined using a biochemical analyzer. Results. In rats of the 5th group (-B-D-Ca-Mg), there were 3.4-fold increase (p<0.05) in iron plasma level, 1.7-fold elevation (p<0.10) in alkaline phosphatase activity, and 1.8-fold decrease (p<0.05) in alanine aminotransferase (ALT) activity on the background of the increase in α-tocopherol blood plasma level by 26.7% (p<0.05) and liver content by 2.0 fold (p<0.05) relative to the indicators in animals who hadn't passed the deficiency of micronutrients (Control) and / or from the 2nd group (+B+D+Ca+Mg). The lack of B group vitamins in the diet, which persisted during the correction of vitamin D, calcium and magnesium deficiency in rats of the 3rd group (-B+D+Ca+Mg), inhibited the recovery of diagnostically significant biochemical parameters of blood plasma (namely, an increased level of glucose, iron, triglycerides, cholesterol, α-tocopherol, increased alkaline phosphatase activity and reduced ALT activity) to the level in animals of the control group and/or rats fed the diet replenished for all missing micronutrients (+B+D+Ca+Mg). Conclusion. Combined deficiency of several micronutrients led to changes in biochemical blood parameters. Reduced intake of calcium and magnesium during the correction of the lack of vitamins D and B group in the diet can have a negative impact on vitamin B2 status. Even under normal dietary vitamin E intake the combined deficiency of several other micronutrients affected the metabolism of this vitamin (increased levels of vitamin E in the liver and blood plasma of animals). Chronic combined alimentary deficit of B vitamins, calcium and magnesium, which is characteristic in the diet of the Russian population, reduces vitamin D bioavailability, which justifies the expediency of using vitamin-mineral complexes.

The toxic effects of nickel nanoparticles (NiNPs) in their 92-day oral administration to male Wistar rats at doses of 0.1, 1 and 10 mg/kg body weight were evaluated. An increase in glycemia, triglyceride, LDL, total protein, and its globulin fraction levels were noticed in NiNPs exposed rats. NiNPs caused a decrease in reserves of liver glutathione and excretion of selenium in the urine, and an increase in serum levels of cytokines IL-1β, IL-2, IL-6, IL-12p70, TNF-α, and INF-γ, with a simultaneous decrease in IL-17A as well as increased fibrosis-marking gene and Tp53 expression.

This study aimed to evaluate the long-term low-dose effects of exposure to a mixture of 6 pesticide active substances (diquat, imazamox, imazethapyr, tepraloxydin, bentazone, acifluorfen) and to elucidate if chronic vitamin deficiency can influence their toxicity. Two hundred Wistar rats were divided in 4 groups: a vitamin-sufficiency control group, a vitamin-deficiency control group, a vitamin sufficiency test group and a vitamin-deficiency test group. The test groups were treated with the aforementioned pesticides at doses 100 times lower than the corresponding NOAEL. After 6 months, ten rats from each group were sacrificed and a complete evaluation of blood and urine biochemistry, biomarkers of oxidative stress, xenobiotic detoxification enzymes and lysosomal enzymes and organ histopathology was performed. The pesticides mixture and vitamin deficiency determined an increase in alkaline phosphatase levels and urinary calcium levels, abnormal serum lipid profile, and a decrease of total blood proteins levels, red blood cells, haematocrit and haemoglobin. The combination of the two stressors up-regulated CYP1A1, CYP1A2, CYP2B1 and GST levels. This study provides a new proof for the need to move forward from single chemical testing to a more complex approach to account for the multitude of stressors that can challenge the setting of real safety levels.

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.

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.

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.

The results of experimental studies indicate that the preventive and therapeutic effects of polyphenols in obesity are accompanied by a significant decrease in the severity of dysbiosis caused by the predominance of fats and simple carbohydrates in the diet, especially fructose, and the restoration of the functional state of the microbiota. The aim of the work was to study the effect of quercetin and resveratrol - polyphenols, widely represented in the daily human diet, on the activity of bacterial glycosidases in rats receiving diets high in fructose or fat and fructose. Material and methods. Using spectrophotometric analysis, the activity of β-galactosidase (Gal), β-glucosidase (Glu) and β-glucuronidase (Gluс) was studied in the content of the cecum of Wistar rats receiving a semi-synthetic diet and a 20% solution of fructose instead of drinking water (hfr diet) or a semi-synthetic diet with a high (30%) fat content and a 20% solution of fructose instead of drinking water (hf/hfr diet). Results and discussion. Feeding rats with the hfr diet for 20 weeks led to the suppression of Gal activity by 35, Glu by 46 and Gluс by 31%. With the inclusion of quercetin in the hfr diet at a dose of 34 mg/kg b.w. enzyme activity was restored to the control values and exceeded the level of activity in rats fed hfr ration without quercetin by 60, 100 and 47%, respectively, for Gal, Glu, and Gluс. Feeding rats with the hf/hfr diet for 10 weeks did not have a significant impact on the activity of bacterial enzymes. The inclusion of resveratrol in the hf/hfr diet at a dose of 10 mg/kg b.w. resulted in a decrease in Glu activity by 58 and Gluс by 28%, and an increase in resveratrol dose to 100 mg/kg b.w. caused further suppression of Gal activity by 30, Glu by 76 and Gluc by 64% comparative to the activity in rats on the hf/hfr diet without resveratrol. Conclusion. The obtained data suggest that quercetin restores reduced by hfr diet activity of glycosyl hydrolases of the cecum microflora of rats, most likely due to an increase in the representation of the types of enzyme activity carriers. The suppressive effect of resveratrol on the activity of glycosyl hydrolases of the cecum microflora of rats fed a hf/hfr diet may be the result of its direct action on enzymes and is not associated with the effect on the composition of the intestinal microbiota.

The purpose of the study was to determine effects of quercetin on protective capacity parameters in the experiment on rats fed a high fructose diet. Rats of the control group received a semi-synthetic (s/s) diet and water; animals from the 1st experimental group - s/s diet and 20% fructose solution instead of drinking water; rats of the 2nd experimental group- s/s diet with quercetin (0.1% indiet) and 20% fructose solution instead of drinking water for 20 weeks. Parameters of antioxidant status [total antioxidant activity (AOA), the content of malondialdehyde (MDA) and lipids hydroperoxides, the level of reduced and oxidized glutathione, activity of superoxide dismutase, catalase, glutathione peroxidase, paraoxonase-1, hemeoxygenase-1, NAD(P)H-quinone oxidoreductase], the activity of xenobiotic-metabolizing enzymes [CYP1A1, CYP1A2, CYP2B1, CYP3A, UDP-glucuronosyltransferase (UDP-GT) and glutathione transferase] were studied in plasma and liver of rats. Consumption of the high-fructose diet led to changes in some parameters: diminution of AOA in blood plasma, decrease of AOA and MDA level, unsedimentable activity of lysosomal enzymes, increase of the UDP-GT activity in liver. The inclusion of quercetin in the diet did not affect the studied parameters, except for a more pronounced decrease of the unsedimentable activity of lysosomal enzymes in rat liver. The results of the study indicated that there was no significant effect of quercetin on the protective capacity of rats at the initial stage of obesity caused by high-fructose diet.

Metabolic syndrome (MS) is one of the leading causes of non-infectious pathology among the population of developed countries. It is necessary to have experimental in vivo models of MS for pre-clinical testing of new approaches to its dietary therapy. The purpose of the study was a comparative analysis of functional, biochemical and vitamin markers that characterize the effect of diets with different composition of simple carbohydrates (sugars) on female Wistar rats and female C57Black/6J mice. Animals of each species (n=80) were divided into 5 groups of equal numbers. The animals of the 1st (control) group received a balanced semi-synthetic diet, and the animals of groups from the 2nd to the 5th - the same diet and 30% solutions of sugars - glucose (Gl), fructose (Fr), equimolar mixture Gl and Fr and sucrose instead of water, in the regime of free access for up to 133 days. Measured values included blood pressure, mass of internals, biochemical parameters of blood plasma, the activity of CYP1A1, CYP1A2, CYP2B1, CYP3A and glutathione transferase (GT) in liver, glutathione peroxidase (GP) in erythrocytes, the content of vitamins A and E in blood plasma and in liver, the level of vitamins B1 and B2 and nicotinamide coenzymes in liver. Interspecific differences in the response to sugars manifested in a decrease in the solid diet consumption in mice (in contrast to rats), so that the total consumed energy value in experimental groups of mice did not differ systematically from control, and the weight gain was reduced. Liver was the most sensitive organ to addition of sugars in both rats and mice with mass significantly increasing by the 2nd and the 4th months of the experiment. Hyperglycemia and triglyceridemia were the most noticeable in rats receiving Fr. The concentration of phosphorus increased significantly in blood plasma of all rats groups that received sugars. In rats there was a decrease in the activity of CYP1A1 and CYP1A2 in groups 3 and 5, the activity of CYP2B1 in groups 2 and 5, the increase in HT activity in groups 2, 4 and 5, and GP in group 3 at 56th day of experiment. There was a significant decrease in this index in group 3 at the 56th and the 133rd days of the experiment, and in groups 4 and 5 - at the 56th day. Plasma tocopherol to triglycerides ratio decreased in rats of group 3 at the 56th and 133rd days, groups 4 и 5 - at 56th day, which indicated the decrease of vitamin E safety. Sugars consumption suppressed retinol palmitate accumulation in the liver of rats and mice, and alpha-tocopherol in mice. It was concluded that Fr had the greatest effect on the studied indicators of the organism, and the rats showed the most significant similarity with the clinical picture of MS.

The purpose of the study was to determine the effects of curcumin (CUR) and quercetin (QUER) on the expression of genes and activity of prototypical Nrf2/ARE- and AhR/ XRE-regulated enzymes. Investigation was carried out on male Wistar rats with initial body weight (230-235 g b.w.) that received for 14 days CUR (200 mg/kg b.w.) and QUER (200 mg/kg b.w.) separately or in combination within the standard semi-synthetic diet. The expression of genes and activity of Nrf2/ARE - regulated enzymes - heme oxygenase- 1(HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), AhR/XRE-regulated CYP1A1, CYP1A2 enzymes and the mRNA level of transcription factors Nrf2 and AhR were determined in rats liver. Also the expression of gene CYP3A1 and activity of CYP3A, UDP-glucuronosyltransferase, glutathione transferase were studied in rats liver. Along with this the total antioxidant activity (AOA), malondialdehyde and lipid hydroperoxides levels were determined in blood plasma and liver. The reduced and oxidized glutathione level, total and unsedimentable activity of lysosomal enzymes were investigated in rats' liver. QUER, especially in combination with CUR, increased the AOA of blood plasma and reduced the content of lipid hydroperoxides in it. CUR and QUER did not affect NQO1 activity, but the combined action caused an increase in the HO-1 activity without affecting the expression of the corresponding gene (Hmox1) and Nrf2 gene. CUR and, to a lesser extent QUER, had a strong inducing effect on CYP1A1, CYP1A2, CYP3A activity, but only the CYP1A1 activation was accompanied by the induction of CYP1A1 gene. The inducing effect of CUR and QUER on the activity of CYP450 enzymes greatly enhanced by their combined action. Membrane stabilizing action of CUR and QUER was also strongly expressed under its combined intake. Thus, we can conclude that CUR and QUER, especially in combination, contribute to the protective and adaptive capacity.

Flavonoids rutin (R) and hesperidin (Hes) have a broad spectrum of the biological activity based on their antiradical properties and ability to increase the activity of antioxidant enzymes, including the activity of heme oxygenase-1 (HO-1) and NAD(P)H-quinone oxidoreductase (QR). It is supposed that the main regulator of the activity of HO-1 and QR is the transcription factor Nrf2. The purpose of the study was to determine the effects of R and Hes on the expression of Nrf2 gene and protein, on the activity and mRNA and protein expression of HO-1 and QR at their separate and combined action. Administration in diet of male Wistar rats (with initial body weight 180-200 g) R (400 mg/kg b.w.) and Hes (400 mg/ kg b.w.) during 14 days separately or in combination had no toxic or pro-oxidant effect, which were assessed by the level of liver MDA, hydroperoxides of lipids, reduced and oxidized glutathione. R and, to a lesser extent, Hes caused increased activity of HO-1 and QR. Their combined effect on the activity of HO-1 did not differ from the separate effect of each flavonoid. The combined action of R and Hes on the activity of QR was additive. According to Western blotting, changes in HO-1, Nrf2 and QR protein levels under the action of R and Hes separately or in combination were not statistically significant. The results of real time PCR demonstrated the presence of small, but statistically significant, changes in the level of expression of the genes Nrf2 (Nrf2), HO-1 (Hmox1) and QR (NQO1) both for separate and combined action of R and Hes. Thus, the obtained results showed that high-dose of R and Hes separately and in combination didn't significantly affect the gene and protein expression of transcription factor Nrf2 and that the increased activity of HO-1 and QR was not associated with the increased expression of Hmox1 and NQO1 genes.