Indices In Rats Research Articles

Low polarity fraction of Radix Bupleuri alleviates chronic unpredictable mild stress-induced depression in rats through FXR modulating bile acid homeostasis in liver, gut, and brain

Radix Bupleuri (BR, Bupleurum chinense DC.) is a well-known traditional Chinese medicine (TCM) known for its effects on soothing the liver and alleviating depression, and is widely used in clinical settings to manage depressive symptoms. A dosage of 12.5g crude drug/kg/d of the low-polarity fraction of Radix Bupleuri (LBR) demonstrated effectiveness in treating depression in our previous study. However, the mechanism through which BR ameliorates depression remains unclear. This study aimed to explore the polar fractions of BR and their mechanisms of action in the treatment of depression. Chronic unpredictable mild stress (CUMS) rats were continuously administered BR by oral gavage for 4 weeks. Behavioral and biochemical indicators were evaluated to assess the antidepressant effects of LBR, and transcriptomics was used to explore the relevant pathways. In addition, pseudo-targeted bile acid (BA) metabonomics was used to quantify the BA profiles. Molecular biology techniques have been used to investigate the underlying mechanisms. LBR serves as a more effective active fraction with antidepressant activity. Intervention with LBR, which is characterized by a clearly defined chemical composition, significantly ameliorated depression-like behavior and biochemical indicators in rats subjected to CUMS. Notably, marked improvements were observed in the levels of total bile acids (TBAs) in the blood, liver, and ileum. Mechanistically, liver transcriptome analysis suggested that bile secretion may be a crucial pathway for alleviating depression after LBR treatment. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) BA metabonomics indicated that TCA, β-MCA, γ-MCA, Tβ-MCA, and UDCA in the liver, Tβ-MCA, TCA, βMCA, GHDCA, and GLCA in the ileum, and β-MCA, CA, and DCA in the hippocampus were the potential therapeutic targets. In addition, molecular biology experiments showed that LBR exerts antidepressant effects by regulating the FXR/SHP/CYP7A1 pathway in the liver, the FXR/FGF15/ASBT pathway in the ileum, and the FXR/CREB/BDNF pathway in the hippocampus. In conclusion, LBR attenuated depression by moderating BA homeostasis through FXR and related genes within the liver-gut-brain axis.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Analytical and quantitative assessment of the structural components of the adrenal glands of rats under the conditions of exposure to the venom of vipers Vipera berus berus and Vipera berus nikolskii

Snakebite envenoming is a common but neglected public health problem worldwide, especially in tropical countries. Annual mortality as a result of snakebites exceeds 138,000. It is believed that this problem is underestimated, and in many countries, individual cases of bites are not subject to proper fixation. The purpose of the study is the analytical and quantitative assessment of the structural components of the rats' adrenal glands under exposure to the venom of Vipers Vipera berus berus and Vipera berus nikolskii. Experimental studies were carried out on white, non-linear male rats. Vipera berus berus and Vipera berus nikolskii viper venom were obtained from V. N. Karazin Kharkiv National University. The freeze-dried native venom was stored at -20 °C and dissolved in saline immediately before the experiment. The animals were divided into three groups (control and 2 experimental groups) of 10 individuals each. Experimental rats were injected intraperitoneally in a physiological solution with a semi-lethal dose (LD50) (1.576 mg/g-1) of Vipera berus berus and Vipera berus nikolskii venoms. Animals of the control group were injected intraperitoneally with only a physiological solution. Rats were removed from the experiment 24 hours after exposure to the poison and anesthetised by cervical dislocation. Statistical analysis of the area of the microcirculatory channel and the nuclear-cytoplasmic index was performed using Fiji: ImageJ program and processed in Excel. Administration of the venom of the vipers Vipera berus berus and Vipera berus nikolskii to rats was accompanied by a significant increase in the area of the microcirculatory bed relative to the control group (2.9 times for Vipera berus berus and 6.5 times for Vipera berus nikolskii). Exposure to Vipera berus berus viper venom was associated with a significant decrease in the nuclear-cytoplasmic index in rats of the experimental group compared to the control group (13 % and 42 %, respectively), which is evidence of a decrease in the area of the nuclei of endocrinocytes of the adrenal cortex. This indicator in rats under the administration of Vipera berus nikolskii venom was even lower and amounted to 12 %. According to the statistical analysis of the quantitative assessment of the state of the cortical substance of the adrenal glands, it is worth noting the similar effect of the poisons of both types of snakes at the cellular level. At the same time, at the tissue level, the effect of Vipera berus nikolskii venom is more pronounced than that of Vipera berus berus - this is evidenced by the higher degree of disruption of the structure of the hemomicrocirculatory channel in the adrenal cortex of animals from the group that was affected by this venom. It led to an increase in the area of vessels due to their expansion and ruptures of their walls and haemorrhages into the surrounding parenchyma and stroma.

Identification of Central Genes and Regulatory Pathways Associated with Hyperlipidemia in Rats.

Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases. The transcriptomic data and the gene regulatory networks of hyperlipidemia are largely unclear. We analyzed the changes in liver gene expression and the serum levels of biochemical indicators in rats with hyperlipidemia induced by high-fat diet (HFD). The body weight, liver weight, and the serum levels of TG, TC, HDL-C, LDL-C, ALT, and AST were significantly higher in the hyperlipidemic rats compared to the healthy controls (P < 0.05). In addition, HFD feeding decreased the antioxidant capacity of the liver tissues and significantly increased the arteriosclerosis index (AI) (P < 0.05). There were 584 differentially expressed genes (DEGs) in the hyperlipidemia model compared to the control, with |log2FC|≥ 1 and P-adjust ≤ 0.05 as the thresholds. GO analysis of the DEGs revealed significant enrichment of 382 biological processes (BP), 18 cellular components (CC), and 40 molecular functions (MF). In addition, pathways related to bile secretion, cholesterol metabolism, and steroid hormone biosynthesis were significantly associated with hyperlipidemia. The key genes potentially involved in the blood lipid changes were Agt, Src, Gnai3, Cyp2c7, Cyp2c11, Cyp2c22, Apoa1, Apoe, and Srebf1. The genes and pathways identified in this study are potential intervention targets for hyperlipidemia and warrant further investigation.

Comprehensive fecal metabolomics and gut microbiota study of the protective mechanism of herbal pair Polygonum hydropiper-Coptis chinensis in rats with stress-induced gastric mucosal damage.

Introduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites. Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation. Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone. Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats.

To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

Effects of rotating electric fields on blood metabolic indicators: an experimental study

BACKGROUND: Stress is an integral part of life in both humans and animals. Up to 70% of the Russian population have reported a certain degree of stress associated with approximately 80% of diseases. This heavy burden of stress explains a significant body of research on the issue of stress and its associations with health indicators. AIM: To study the effects of rotating electric fields on blood metabolic parameters in experimental animals with different levels of resistance to stress. MATERIALS AND METHODS: A total of 54 non-inbred white male rats comprised the sample. We measured serum levels of 11-hydroxycorticosteroids, glucose, C-reactive protein, total sialic acids and the activity of hepatospecific enzymes, such as aspartate transferase, alanine transferase, and alkaline phosphatase at the 10th and the 20th day of exposure to a man-made rotating electric field and in the non-exposed control group. By the level of resistance to stress all rats were divided into stress-resistant, stress-unresistant and ambivalent groups using the "open field" method. RESULTS: On the 10th day of exposure, the levels of 11-hydroxycorticosteroids, glucose, C-reactive protein, total sialic acids increased in all three groups of animals. The activity of aspartate transferase, alanine transferase, and alkaline phosphatase also increased in all rats. On the 20th day, the studied parameters remained elevated compared to the control group. The most pronounced changes were observed in the group of stress-unresistant individuals. CONCLUSION: Our results demonstrate significant effects of rotating electric fields on blood metabolic indicators in rats. The degree of change depends on individual level of stress resistance.

EFFICACY OF A DCBRN-01VN SKIN DECONTAMINANT ON ANIMALS EXPOSED TO 2-CHLOROETHYL ETHYL SULFIDE

Chemical warfare agents are an actual threat and decontamination for victims is a main concern when mass exposure occurs. The study evaluated the effectiveness of the skin decontamination agent DCBRN-01VN based on the oxime compound KBDO for CEES (2-chloroethyl ethyl sulfide). HPLC analysis method was used to determine the temperature after decontamination in vitro and in vivo tests and then to check biochemical and hematological indicators in rats. The test results show that DCBRN-01VN has a high efficiency of CEES decontamination, in vitro: with the ratio of CEES: decontaminant 1:20 in 10 minutes reaching 55.04%, with the ratio 1:10 in 20 minutes reached 55.95%, in 30 minutes reached 82.93%, in 60 minutes reached nearly 100%; in vivo test with a ratio of 1:15 in 20 minutes reached almost 100%. Results of biochemical and hematological examination showed no difference between the negative control group and two experimental groups (with decontamination and without decontamination) P(2-1) &gt; 0.05; P(3-1) &gt; 0.05. Histopathological analysis showed that decontamination also reduced damage caused by CEES.

Serum biochemical indicators in rats of different ages after replacing femoral metaphysis defects with allogeneic bone implants saturated with mesenchymal stem cells

The aim of the study: to evaluate the course of metabolic processes after replacing femoral metaphysis defects with allogeneic bone implants saturated with allogeneic mesenchymal stem cells (MSCs) based on the analysis of serum biochemical indicators of connective tissue metabolism in laboratory rats. Material and methods. A critical-sized transcortical femoral defect model in the femur metaphysis of white rats was used. Blood serum concentrations of glycoproteins, total chondroitin sulfates, total protein and calcium, alkaline and acid phosphatase activity were measured. Results. On the 28th day, in 3-month-old animals with MSC, in comparison with the data of rats without MSC, clear signs of connective tissue formation and bone resorption activity were observed, as evidenced by an increase in serum chondroitin sulfates and acid phosphatase activity. On the 90th day, this group of rats under the influence of MSCs showed signs of decreased bone tissue formation with lower serum activity of alkaline phosphatase. In 3-month-old rats with MSC, signs of the inflammatory process chronization with higher serum concentrations of glycoproteins were detected on the 90th day of the experiment in comparison with data from animals without MSC. In 12-month-old rats with MSCs, signs of bone resorption were documented on the 14th day, which were manifested by a higher serum activity of acid phosphatase with less formation of connective tissue and lower concentrations of chondroitin sulfates. On the 28th day, the effect of MSCs in 12-month-old animals was manifested in the form of a slowdown in bone formation with a decrease in alkaline phosphatase activity. On the 90th day, the connective tissue formation was activated with higher concentrations of chondroitin sulfates in these animals. Conclusions. The studied biochemical indicators in 3-month-old animals showed greater lability. The regeneration phases were faster in 3-month-old animals as well as in animals with alloimplants without MSCs. Injections of allogeneic MSCs together with an allograft immediately after a bone damage, regardless of age, caused signs of bone formation slowing and excessive formation of connective tissue, therefore, the combination of allogeneic MSCs with an allogeneic bone implant is not advisable to use in fresh fractures.

EFFECT OF MELATONIN ON FIBRINIOLYSIS IN THE BRAIN OF RATS WITH DEXAMETHASONE DIABETES

The purpose of our study was to determine the effect of melatonin on the characteristics of fibrinolysis in the brain 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 rats were divided into three groups: 1) intact animals (control group); 2) rats with untreated dexamethasone diabetes; 3) rats, what were administered by melatonin in a dose of 10 mg per kg of body weight intragastrically daily through a metal probe during the 13 days of experiment in addition to dexamethasone injection. Results. In the cerebral cortex of rats with diabetic neurodegeneration on the 14th day of the experiment, an increase in total fibrinolysis due to enzymatic fibrinolysis was found. Thus, TFA increased by 10%, and EFA by 15% compare to the indicators of animals of the control group. In the hippocampus, NFA indicators did not change, and EFA increased by 25% compared to the indicators of control group. Daily oral administration of melatonin (10 mg/kg) to rats with diabetes-induced neurodegeneration did not significantly affect the EFA index in the cerebral cortex, but contributed to a 15% decrease in this indicator in the hippocampus, compared to the indicators of diabetic rats that did not receive any correction agents. The indicators of TFA and NFA both in the cerebral cortex and in the hippocampus were not significantly different from the indicators of rats with diabetes. Conclusions. A decrease in the intensity of the fibrinolysis process was noted in the cerebral cortex and hippocampus of rats that, in addition to dexamethasone injections, were orally administered melatonin daily for 13 days.

Kısıtlama ve Soğuk Kısıtlama Stresinin Wistar Albino Sıçanlarda Pıhtılaşma Göstergeleri Üzerindeki Etkileri

The purpose of this study was to investigate the effects of two different acute stress protocols, such as restraint and cold restraint stress, on coagulation indicators in rats. The study was conducted in 18 male Wistar albino rats aged 8-10 weeks with a body weight of 180-220 g. After a one-week adaptation period, the rats were randomly divided into three groups (n=6/group). The animals in the control group were not exposed to any stress. Rats in the restraint group were housed in restrainer designed for rats, and their movement was restricted for 2 hours at room temperature. Rats in the cold restraint group were kept in the restrainer at +4°C for 2 hours. Blood samples were collected by cardiac puncture under ketamine and xylazine anesthesia in Vacutainer® tubes containing 3.2% sodium citrate (0.109 M trisodium citrate). Coagulation indicators (aPTT, PT, INR, fibrinogen, and D-dimer) were analyzed using an automated analyzer (Roche Cobas t511, Switzerland). Although acute stress (restraint and cold restraint stress) had no effect on aPTT and D-dimer levels (p&gt;0.05), it increased PT and INR values (p

Euphorbium total triterpenes improve Freund's complete adjuvant-induced arthritis through PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathways.

Euphorbium is the resinous secretion of Euphorbia resinifera Berg. According to the record, Euphorbium was first used by Roman doctors to treat the emperor's joint pain. In China, it is applied in folk medicine to treat damp-cold or mucous diseases, such as arthralgia and ascites, etc. This herb is used for rheumatoid arthritis and skin tumors in the folklore of northeastern Brazil. Triterpenes are mainly characteristic constituents of Euphorbium, and possibly possess anti-rheumatoid arthritis. To explore the preventive effect of Euphorbium total triterpenes (TTE) on Freund's complete adjuvant (FCA) induced arthritis in rats and its mechanism. TTE was extracted and isolated from Euphorbium, and its components were analyzed by HPLC. The safety of TTE was evaluated by an acute toxicity test in mice. Arthritis was induced in rats by injecting 0.2mL FCA into the right hind paw toe, except for the control group, which was given the same volume of physiological saline. Tripterygium Glycosides (TG, 7.5mg/kg) and TTE (32, 64 and 128mg/kg) were administered by gavage for 30 days. Body weights, paw swelling, and arthritic scores were measured during the experiment process. After 30 days, blood and joints were harvested to determine various indicators of arthritis. The contents of euphol and euphorbol in TTE were 47.03% and 18.77% respectively, and the maximal feasible dose of TTE in mice is 12 g/kg. The experimental results showed that arthritis indicators in rats deteriorated after FCA inducement compared with the control group. After treatment with TTE, the swelling degree and histopathological change of the hind paws in rats were significantly improved as well as arthritic score; the serum TNF-α, CRP, IL-1β, IL-6, IL-18 and RF levels in rats were significantly reduced; The expression of PI3K, AKT, P-AKT, Bcl-2, NF-κB, NLRP3 and Pro-caspase-1 protein in joint tissue were down-regulated, and the expression of Bax protein was up-regulated. The results suggested that TTE possessed anti-arthritis effects, and its mechanism may be related to its anti-inflammatory and immunomodulatory properties, as well as regulation of PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathway.

Flammulina velutipes polysaccharide-iron(III) complex used to treat iron deficiency anemia after being absorbed via GLUT2 and SGLT1 transporters

Iron deficiency anemia (IDA) is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex (FVP1-Fe(III)) in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(III) was mediated by sodium-dependent glucose transporter-1 (SGLT1) and facilitated glucose transporter-2 (GLUT2) and GLUT2 played a dominant function. The multidrug resistance-associated protein-2 (MRP-2) was involved in the efflux of FVP1-Fe(III) across the Caco-2 cells. In vivo, FVP1-Fe(III) had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(III) could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C (vit C) could enhance the therapeutic effect of FVP1-Fe(III). These present findings showed that FVP1-Fe(III) could be exploited as a novel iron supplement to treat IDA.

Changes of electrocardiograms of animals with epinephrine heart damage in influences of stress and castration

Changes of electrocardiograms of animals with epinephrine heart damage in influences of stress and castration

Effect of ethylthiosulfаnylate in combination with vitamin E on certain biochemical blood parameters and hematological indicators in rats under the influence of Cr(VI)

The aim of our study was to investigate the effect of ethylthiosulfаnylate, a representative of the class of thiosulfonate compounds, in combination with vitamin E on certain biochemical blood parameters, hematological indicators and total Chromium content in liver of rats exposed to Cr(VI). Laboratory rats were divided into 8 groups of 5 animals each. Animals of group I (intact control) were injected daily intraperitoneally with 150 μl of physiological saline solution for 7 days. Rats of III/IV groups received intraperitoneal daily administration of K2Cr2O7 (diluted in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg) for 7/14 days. Animals of the II experimental group were injected daily intragastrically with 1000 μl of sunflower oil for 14 days. Rats of V/VI experimental groups were administrated daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg)/vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days. Animals of VII/VIII experimental groups were injected daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days, after which a 7-day/14-day period of intraperitoneal K2Cr2O7 administration was performed. Exposure to Cr(VI) led to a decrease in the number of erythrocytes, leukocytes, content of hemoglobin, phospholipids, total protein against the background of the accumulation of total lipids, mono- and diglycerides, non-esterified fatty acids, and creatinine in blood of rats. Chromium concentration significantly increased in the liver of rats after administration of Cr(VI). The combined effect of vitamin E and ethylthiosulfаnylate contributed to the partial compensation of Cr(VI)-induced disturbances of the number of leukocytes and content of total proteins, phospholipids, non-esterified fatty acids in blood of rats. Vitamin E and ethylthiosulfаnylate pretreatment also contributed to the reduction of the percentage accumulation of Chromium in liver of rats injected with Cr(VI).

Bioactive compounds anthocyanins as a factor in the nutritional recovery of the body's adaptive potential after intense physical activity in the experiment: assessment of immunological and hematological indicators of adaptation

Restoring the adaptive potential of an athlete is of paramount importance not only for the implementation of his training and competitive activities, but also for maintaining health. One of the leading place in complex recovery programs in sports is given to full-fledged optimal nutrition, which provides for meeting the body's requirements not only in energy, macro- and micronutrients, but also in minor bioactive compounds. The use of anthocyanin-containing products is a promising strategy for the normalization of metabolic and immune disorders that develop as a result of intense physical and neuro-emotional stress not only in athletes, but also in other groups of people exposed to these factors, including military personnel undergoing training in conditions close to combat. This determines the relevance of this study. The aim of the research was to study the effect of an anthocyanin-enriched diet on hematological profile and cellular immunity in rats after intense physical activity. Material and methods. The experiment was carried out for 4 weeks on 4 groups of male Wistar rats with an initial body weight of ~300 g. The motor activity of the animals of the 1st (control) and 2nd groups was limited by the standard keeping animals in the vivarium, while physically active rats of the 3rd and 4th groups received additional physical activity - training on a treadmill. Before the end of the experiment, the animals of 3rd and 4th groups were given debilitating physical activity on a treadmill (until the rats refused to continue the exercise). Rats of all 4 groups received a standard semi-synthetic diet, water ad libitum. Animals in 2nd and 4th groups were additionally fed blueberry and blackcurrant extract (30% anthocyanins) as part of the diet at a daily dose of 15 mg anthocyanins/kg body weight. Hematological parameters were determined on a Coulter ACT TM 5 diff OV hematological analyzer. Expression of CD45R, CD3, CD4, CD8a, CD161 receptors on rat peripheral blood lymphocytes was determined by direct immunofluorescent staining of whole blood cells using a panel of monoclonal antibodies conjugated with fluorescent dyes: APC, FITC, PE. The measurements were carried out on an FC-500 flow cytometer. Results. Intense physical activity in rats of the 3rd group did not lead to a significant change in erythrocyte parameters compared with the control group. Enrichment of the diet with blueberry and black currant extract (the 2nd and the 4th groups) provided a significant (p<0.05) increase in blood content of hemoglobin (Hb) (150.7±0.9 and 154.4±2.0 vs 145.4±0.9 g/l in control), hematocrit (44.95±0.21 and 46.18±0.64 vs 43.78±0.32%) and the average content of Hb in erythrocytes (18.00±0.20 and 18.03±0.24 vs 17.35±0.24 pg). The absolute content of leukocytes and other cellular elements of the leukocyte formula, as well as leukocyte indices in rats of the experimental groups didn't significantly differ from those of the control rats, which confirms the absence of an inflammatory process. Intense physical activity and anthocyanin enrichment of the diet didn't have a significant effect on rat platelet parameters. Enrichment of the diet of rats of the 4th group with blueberry and black currant extract led to the activation of cellular immunity, as evidenced by a significant (p<0.01) increase in the percentage (from the total content of T-lymphocytes) of T-helpers (70.13 ±1.34 vs 63.75±0.99%) and a decrease in the relative content of cytotoxic T-lymphocytes (28.65±1.38 vs 34.71±0.95%) in comparison with those in rats of the 3rd group and at the level of the trend (р<0.1) - from the 1st group indexes (66.87±1.20 and 31.87±1.26%, accordingly). Intense physical activity led to a decrease in immunoregulatory index in rats of the 3rd group (1.86±0.07) compared with the control (2.13±0.12) (p<0.1), and in animals of the 4th group this indicator was significantly higher (2.50±0.14, p<0.05). In animals of the 3rd group a statistically significant (p<0.05) decrease in the relative content of NK cells in peripheral blood was found compared to the control. Enrichment of the diet of physically active rats with blueberry and black currant extract led to a significant (p<0.05) increase in the percentage of NK cells compared to this indicator in rats of the 3rd group (4.87±0.75 vs 2.08±0.18%) and had no significant difference with the indicator in rats of the control group (4.32±0.98%). Conclusion. The enrichment of the rats' diet with blueberry and blackcurrant extract containing a daily dose of 15 mg of anthocyanins per kg of body weight provides an increase in blood Hb content, hematocrit and the average content Hb in erythrocytes. It has been established that intense physical activity induces the cellular immunity suppression. The activating effect of anthocyanins on adaptive cellular immunity and NK cells, which are lymphocytes of innate immunity, was revealed. The data obtained indicate the effectiveness of the use of bioactive compounds (anthocyanins) to increase the adaptive potential of the organism.

Effect of Uremic Clearance Granules on improvement of chronic kidney disease in rats based on microbiome-metabolomics and its mechanism

This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.

EFFECT OF DRY EXTRACT FROM REISHI MUSHROOMS ON THE STATE OF ANTIOXIDANT SYSTEM IN RATS WITH DMH-INDUCED COLON CARCINOGENESIS.

The aim: To study pro- and antioxidant systems indicators in rats with chemically induced colon carcinogenesis on the background of the reishi mushrooms dry extract use. Materials and methods: The study was performed on 120 white male rats. Chronic oncogenic intoxication was modeled by administering 1,2-dimethyl¬hydrazine (DMH) hydrochloride for 30 weeks (1 time per week). A dry extract from the reishi mushrooms was administered intragastrically daily at a dose of 100 mg/kg of the animal's body weight. Blood and liver samples were taken for research monthly. The state of the pro- and antioxidant systems was studied by the content of oxidative modification of proteins products, superoxide dismutase and catalase activity, contents of reduced glutathione and ceruloplasmin. Results: An increase in the activity of free radical oxidation processes after DMH-induced colon carcinogenesis in rats is evidenced by a decrease in the super-oxide dismutase activity, catalase activity, content of reduced glutathione, an increase in the content of ceruloplasmin and products of oxidative modification of proteins in the blood serum and liver of animals. The effectiveness of the dry extract of reishi mushrooms and its positive effect on the state of pro- and antioxidant systems was experimentally proved. Conclusions: The use of the dry extract of reishi mushrooms under conditions of DMH-induced colon carcinogenesis in rats led to normalization of the anti¬oxidant protection system state and the reduction of oxidative stress.

Succinate dehydrogenase as a new target for melatonin binding in the complex diabetes mellitus treatment

Relevance. Alloxan, destroying the beta cells of the pancreas, provokes hyperglycemia, which causes a hypoenergetic state. Mitochondrial succinate dehydrogenase dysfunction plays an important role in the pathogenesis of diabetes. Pharmacotherapy of diabetes mellitus has been and remains the subject of numerous studies. Recently, the attention of researchers is increasingly attracted by the hormone of the pineal gland - melatonin, due to its biological and pharmacological properties. The aim of the study was to study the effect of melatonin on the activity of succinate dehydrogenase as a new target in experimental alloxan-induced diabetes mellitus. Materials and methods. The studies were carried out on male Wistar rats, with an average mass of 120-150 g, which were kept on a standard diet. The animals were divided into 4 groups. The control group was injected with saline solution, the second group was injected with melatonin at a dose of 1 mg/kg daily for 14 days, experimental diabetes in animals was simulated by intraperitoneal administration of alloxan at a dose of 150 mg/kg with diabetes. The fourth group of animals received melatonin on the background of alloxan. Succinate dehydrogenase activity was determined in liver and pancreatic tissues by photometric method. For the docking analysis, the AutoDock Vina and AutoDock Tools software packages were used. Results and Discussion. According to the results obtained, reciprocal relationships arise under the influence of alloxan in the activity of SDH in the liver and pancreas. Alloxan causes an increase in the activity of SDH in the liver by 1.9 times, and in the pancreatic tissue there is a significant decrease - by 5 times. The use of melatonin for animals with alloxan diabetes led to a decrease in the activity of succinate dehydrogenase in the liver by one and a half times in comparison with the indicators of rats with alloxan diabetes. In the pancreas, on the contrary, the activity of the enzyme increased by 3.3 times, which may indicate the restoration of the function of Langerhans beta cells. Conclusion. Melatonin blocking succinate dehydrogenase domain A reduces the hyperactivity of the enzyme in the liver, and in the pancreas through its specific receptors (MR1 and MR2) present on the surface of the membranes of β- and α-cells directly interferes with the function of the cellular elements of the islets of Langerhans, restoring them.

Baicalin regulates TLR4/IκBα/NFκB signaling pathway to alleviate inflammation in Doxorubicin related cardiotoxicity

Cancers and the toxic and side effects of their treatment have always been a major problem for human beings. Doxorubicin (DOX) is one of the classical anthracycline antineoplastic drugs, but it can cause different degrees of heart damage and even serious heart failure. The incidence of myocardial toxicity increased significantly when the cumulative dose of the drug was more than 550mg/m2, and the relevant mechanism was related to the inflammatory reaction, reactive oxygen species and the apoptosis of cardiomyocytes in the myocardium. Relevant studies have shown that baicalein (Ba) can inhibit NFκB-related inflammatory signaling pathway protects cardiac function, but whether it can inhibit DOX induced cardiotoxicity has not been reported. Therefore, in animal studies, we explored the effects of doxorubicin and baicalein on cardiac function, TLR4/IκBα/NFκB signaling pathway and related inflammatory indicators in rats. In cell experiments, by silencing or overexpressing TLR4, we explored whether baicalein could achieve anti-inflammatory effect through regulating TLR4/IκBα/NFκB signaling pathway and ultimately inhibit doxorubicin induced cardiotoxicity.