Body Weight Of Animals Research Articles

Efficacy and safety of nanoparticles of glibenclamide and organomodified layered double hydroxides in diabetics rats

Glibenclamide (GB) is an important drug in the treatment of type II diabetes mellitus (DM II); however, its low solubility causes variability in its oral bioavailability, negatively affecting the pharmacological treatment. Nanoparticles (NP) of GB and organophilized Layered Double Hydroxide (LDH) were developed to improve oral bioavailability and tested in streptozotocin-induced diabetic rats to evaluate therapeutic efficacy and safety. Blood glucose was measured for 12 h or after 28 days of treatment. In addition, body weight, water and feed consumption, hematological, biochemistry and morphological parameters and markers of oxidative stress were determined. After the treatment, GB with LDH normalized the blood glucose level, indicating a better release profile. Water and feed intake and body weight of animals treated with GB and GB with LDH were closer to the normoglycemic group and did not indicate signs of toxicity of the nanoparticles. The biochemical, hematological and histological results also showed no significant changes related to nanotoxicity. The combination of GB with LDH proved to be critical in the oxidative balance, as it reduced the oxidative stress of vascular tissue. In conclusion, NPs are a potential controlled release system for the treatment of DM II.

Morphological spectrum of the blood of hypotrophic calves against the background of the use of the drug interamin

The aim of the work is to study the effect of the complex drug interamin on the morphological blood indicators of calves with signs of antenatal hypotrophy. The object of the study were newborn calves, which were divided into 4 groups. The calves of the first experimental group (n=10, hypotrophic calves) were administered the complex drug interamin subcutaneously, five times on days 1, 3, 8-14, 18-24 and 56-60 of life at a dose of 1 ml per 10 kg of animal body weight. The calves of the second experimental group (n=10, hypotrophic calves) were administered "Biferon-B" subcutaneously, according to the above scheme. The calves of the third (n=10, negative control, hypotrophic calves) and fourth (n=10, control, normotrophic calves) groups were not treated with drugs. On the first day after birth, as well as on days 7, 30 of life and 5-10 days after the transfer to the rearing group, venous blood samples were taken from calves to assess its morphological composition. It has been established that hematological failures develop the calves with antenatal hypotrophy, manifested in the form of hypochromic anemia and a tendency to pancytopenia. The use of the drug interamin contributed to the activation of hematopoietic processes in calves with signs of antenatal hypotrophy. Thus, the number of erythrocytes in calves treated with interamin was significantly higher by 10.2, 7.6, 31.0% than in the calves from the negative control group, and the hemoglobin level from 7 to 60 days of life was within the reference range for these ages of this animal species. At the age of 7 days, against the background of the introduction of interamin, the number of leukocytes also increased by 6.4%, with a decrease in stab neutrophils by 52.5%, and segmented neutrophils – by 20.1%, with an increase in the percentage of lymphocytes by 39.4% relative to those in calves from the negative control group, and did not significantly differ from the indicators of normotrophic calves.

The Effect of Nano Calcium Carbonate and/or Recombinant Bone Morphogenetic Protein as a Biological Orthodontic Retainer on the Body Weight of Experimental Rat.

Retention after orthodontic tooth movement (OTM) is essential to prevent relapse. This study examined the effects of a fixed orthodontic device and Nano Calcium Carbonate (CaCO3) nanoparticles with or without recombinant human bone morphogenetic protein (rhBMP) on rat body weight. OTM was administered for 21 days to 80 Wistar Albino rats. First molar mesialization was active then forming two 40-rat groups which were subdivided into four subgroups of 10 rats each. These subgroups received 5 µg/kg rhBMP, 75 µg/kg CaCO3, 80 µg/kg rhBMP-loaded CaCO3 and one control. The relapse rate was examined weekly over the second 21 days when the second group exhibited mechanical retention and the first did not. Group 1 rats were murdered after 21 days (day 42), whereas group 2 rats entered a third 21-day post-retention period and then murdered (day 63). BW and OTM were measured on days 1, 21, 28, 35, 42, and 63. Within each group, the animal body weight was reduced significantly after the intervention and continued over time with a higher average reduction in the 9-week group than the 6-week group. However, there were no significant (P-value ˃0.05) differences in the BW between the groups of the two (6-week and 9-week) sets and the subgroups of the 6-week set across each time point. In contrast, there was a significant (P-value ˂0.05) difference between the BW of the conjugate subgroup and the other three subgroups in the 9-week set, particularly on 63rd day. CaCO3 nanoparticles and/or BMP with orthodontic treatment collectively or individually cause a reduction of body weight in rats.

Effects of a New Kappa Agonist (Fluorophenyl Derivative of Imidazo[1,2-<i>а</i>]benzimidazole) on the Rat Genome

Selective kappa-opioid receptor (KOR) agonists are considered a promising group of substances for developing opioid analgesics characterised with an original mechanism of action without the risk of respiratory depression and drug addiction. Previous studies identified a fluorophenyl derivative of imidazo[1,2-a]benzimidazole (RU-1205) with a KOR-based mechanism of analgesic action established in in vitro and in vivo experiments.The aim of the study was to assess the effect of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-a]benzimidazole dihydrochloride on the level of DNA damage in rats after a single subcutaneous injection.Materials and methods. The study was conducted in adult white outbred laboratory rats of both sexes. DNA damage was estimated using the comet assay. The study involved a single subcutaneous injection of an aqueous solution of RU-1205 in three doses: 1, 10, and 100 mg/kg. The authors used intraperitoneal methyl methanesulfonate (40 mg per kg of animal body weight) as a positive control and 0.9% NaCl (100 μL per 100 g of animal body weight) as a negative control.Results. A single subcutaneous injection of RU-1205 to rats did not produce a significant dose-dependent increase in % tail DNA when compared with the state of the corresponding organ/tissue cell genome in negative control animals after normal saline administration at the same time points. In the negative control groups, % tail DNA in cells of various organs/tissues ranged from 1.83% to 3.82% (median values [25–75%]). On the contrary, the administration of 40 mg/kg of genotoxic methyl methanesulfonate led to an increase in damaged DNA in all studied organs and tissues when compared with negative control animals.Conclusions. The study of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-a] benzimidazole dihydrochloride genotoxicity demonstrated that a single subcutaneous injection of 1, 10, or 100 mg/kg of RU-1205 to rats did not damage the cell genome of the studied organs.

Abstract B026: SIWA318H, a novel advanced glycation end product (AGE) specific antibody, targets cancer and senescent cells in the tumor microenvironment and exhibits potent antitumor activity in a humanized mouse model for pancreatic cancer. [R

Abstract The aging-related and cancer cell derived oxidatively stressed tumor microenvironment drives cell senescence. Senescent cells (SCs), in turn, promote immune suppression, tumor progression, and metastasis. Hence, targeting SCs presents an attractive approach for cancer therapy. SIWA318H is a monoclonal antibody that selectively targets an advanced glycation end product biomarker on the surface of dysfunctional cells exhibiting both (a) aerobic glycolysis and (b) oxidative stress. The SIWA318H biomarker is associated with cancer cells, SCs, oxidatively damaged cells, and infected cells. SIWA318H has been shown to bind to an ADCC inducing human IgG FcγR3 receptor as a mechanism of action. SIWA318H exhibits strong binding to pancreatic cancer patient derived xenograft tumors as demonstrated by immunohistochemistry. In an in vivo study using a humanized mouse xenograft model for pancreatic cancer, we showed that treatment with SIWA318H (both high and low dose groups) statistically significantly reduced tumor growth compared to the isotype antibody control group (P < 0.0001). In addition, there was a significantly higher number of mice had complete remission in the treated groups compared to the isotype control group: 37.5% in high dose group (P = 0.0325) and 43.8% in low dose group (P = 0.0143). Moreover, mice treated with 318H had a median overall survival of > 45 days compared to 26 days for the isotype control mice. There was no difference in animal body weight between the SIWA318H-treated mice and the isotype control mice. Immunohistochemical analysis of tumor tissues taken from the in vivo study showed that SIWA318H treatment significantly reduced (a) tumor fibrosis as measured by the area of αSMA+ staining and (b) the number of senescent cells in the tumor stroma as measured by the number of p16INK4a positive cells in αSMA+ areas. In summary, our results demonstrate that SIWA318H is a novel senolytic antibody that exhibits potent preclinical antitumor activity against pancreatic cancer. SWA318H is currently under development for a first in human clinical trial. Citation Format: Gabriela Rossi, Lewis Gruber, Misty Gruber, Haiyong Han. SIWA318H, a novel advanced glycation end product (AGE) specific antibody, targets cancer and senescent cells in the tumor microenvironment and exhibits potent antitumor activity in a humanized mouse model for pancreatic cancer. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B026.

STAGES OF PRECLINICAL STUDIES OF HERBS EXTRACTS OF ARTEMISIA SPECIES

At the present stage of the development of science, it remains relevant to create new medicines of plant origin with the use of extracts as active substances and improvement of the composition and technology of existing ones.
 The article aimed to highlight the main stages of preclinical studies of herbal extracts of Artemisia species to establish their pharmacological activity, preclinical safety profile, and prospects for further research in developing a medicinal product.
 As a result of the research conducted using the method of generalization and systematic analysis, we identified the main stages of pharmacological research of plant extracts as medicinal substances using the example of Artemisia absinthium L. and Artemisia vulgaris L. extracts.
 Identifying the main stages of pharmacological research of plant extracts is necessary to establish the preclinical profile of the substance's safety, pharmacological effectiveness, and prospects for further study in the development of the medicinal product.
 In the first stage, a toxico-pharmacological study of the extracts is carried out, which includes the study of acute toxicity of the еxtracts. It was established that the intragastric administration of extracts of Artemisia absinthium L. and Artemisia vulgaris L. at a dose of 6000 mg/kg does not lead to the death of animals, which indicates the absence of toxic effects of the extracts in this dose, and characterizes them as practically non-toxic (toxicity class V, LD50 > 5000 mg/kg).
 At the second stage of pharmacological research, the anti-inflammatory activity of Artemisia absinthium L. and Artemisia vulgaris L. extracts was studied (on models of formalin, carrageenan, and zymosan edema). It was established that the sections of Artemisia absinthium L. and Artemisia vulgaris L. showed a pronounced anti-exudative effect throughout the experiment.
 At the third research stage, a study of specific pharmacological activity – hepatoprotective (antioxidant) training was activity.
 It was found that extracts of Artemisia species exhibit hepatoprotective activity in acute toxic liver damage, which leads to a decrease in the intensity of the lipid peroxidation process and a reduction in the harmful effect of tetrachloromethane, bringing the biochemical indicators of blood and liver homogenate of animals to the level of intact animals. The results of the research show that the extract of the herb Artemisia absinthium L. at a dose of 25 mg/kg of the animal's body weight showed a more intense and more effective effect in acute hepatitis compared to the extract of the herb Artemisia vulgaris L. The extract of the herb Artemisia absinthium L. are not inferior to the hepatoprotective effect of the comparative drug "Silibor".
 So, we established a general design of pharmacological research, which included the following stages:
 I stage. Study of the harmlessness of extracts - study of acute toxicity.
 II stage. Study of pharmacological activity of extracts - anti-inflammatory activity.
 III stage. Research of specific pharmacological activity – hepatoprotective (antioxidative) activity.
 Thus, a properly planned preclinical study showed the absence of toxic effects of Artemisia absinthium L. and Artemisia vulgaris L. extracts and the prospect of further pharmacological experiments.

STUDY OF THE HEPATOPROTECTIVE ACTIVITY OF EXTRACTS OF GENTIANA ASСLEPIADEA IN THE ACUTE TETRACHLOROMETHANE HEPATITIS MODEL

Nowadays, diseases of the hepatobiliary system occupy a special place among diseases of internal organs and systems. At present, the most commonly used hepatoprotectors are herbal remedies. Due to the content of flavonoids, polyphenols, trace elements and other groups of biologically active substances, herbal preparations have antioxidant, antiviral, membrane-stabilizing and choleretic effects. Species of the genus Gentiana, whose underground and above-ground parts contain biologically active substances of various chemical structures, are promising for research.
 The aim: to study the hepatoprotective activity of Gentiana аsсlepiadea root extracts on the model of acute tetrachloromethane hepatitis.
 Materials and methods. Hepatoprotective activity was studied on the model of acute tetrachloromethane hepatitis. Experiments were performed on 36 white non-linear sexually mature rats weighing 170-240 g. Animals are divided into 6 groups: 1st group – intact animals; 2nd group – control pathology; groups 3-5 - animals treated with thick and liquid extracts of Gentiana аsсlepiadea; 6th group - animals that received the comparative drug Silymarin. The effectiveness of the hepatoprotective action of the studied extracts was determined by the survival rate of animals, the Liver Mass Coefficient, biochemical parameters of blood serum and liver homogenate.
 Research results. The results of biochemical studies show that a single injection of tetrachloromethane was accompanied by the development of acute toxic damage to the liver in a group of animals with a control pathology, as evidenced by a 3.5 times increase in the activity of alanine aminotransferase (ALT) in blood serum, a 2.45 times increase in the activity of aspartate aminotransferase (AST) and 1.6 times increase in the activity of alkaline phosphatase (ALP), the level of TBK-reactants in blood serum and liver homogenate - 1.8 and 2.5 times, respectively, compared to the indicators of the group of intact animals. The use of extracts of the roots of Gentiana asslepiadea and the comparative drug Silymarin in experimental hepatitis was accompanied by a noticeable decrease in pathological manifestations and led to a significant decrease in the studied parameters relative to the values in animals with control pathology. The most pronounced hepatoprotective activity was established when using thick and liquid extracts of the roots of Gentiana asslepiadea at a dose of 25 mg/kg of animal body weight, as evidenced by a decrease in the activity of the studied enzymes in the blood serum of the experimental animals: by 2.42 and 2.08 times of ALT, by 2.05 and 1.92 times of AST, by 1.44 and 1.37 times of ALP, the level of TBC-reactants in blood serum by 1.75 and 1.58 times, and in the liver homogenate by 1.90 and 1.78 times, respectively. Silymarin had a slightly lower effect on the development of cytolysis syndrome, reducing the activity of ALT by 1.92 times, AST by 1.81 times, ALP by 1.32 times, the level of TBC-reactants in serum and liver homogenate by 1.52 and 1.68 times. The use of Gentiana asslepiadea root extract at a dose of 50 mg/kg of animal body weight did not lead to an increase in hepatoprotective activity.
 Conclusions. In the conditions of acute toxic hepatitis, which is caused by carbon tetrachloride, Gentiana asslepiadea root extracts show a pronounced hepatoprotective activity, which was higher in comparison with the drug Silymarin.

Effect of feeding low protein diets supplemented with selected essential amino acids on growth performance and gut health in early weaned Large White Yorkshire piglets

A study was conducted to assess the effect of feeding low protein diets supplemented with selected amino acids on growth performance and gut health in early weaned Large White Yorkshire piglets. Thirty Large White Yorkshire female piglets belonging to Centre for Pig Production and Research, Mannuthy, weaned at 21 days of age were allotted to three dietary treatment groups (T1, T2 and T3) with five replicates for each treatment. Piglets were fed pre-starter ration till they gained a body weight of 5 kg and then on starter ration from 5 to 18 kg body weight. The dietary protein in treatments T2 and T3 were reduced by 15 and 25 per cent respectively than that of control treatment (T1). Five amino acids viz., lysine, methionine, threonine, valine and isoleucine were supplemented to all treatment groups to meet the requirements as per NRC (1998). Body weights of animals were taken at weekly intervals. There was no significant difference in average body weight among three treatment groups from first to third week. From fourth to eleventh week, the average weekly body weight of T1 was significantly higher than T3. The average daily gain was significantly different among three treatment groups with highest values observed for group T1, followed by T2 and T3. The feed conversion efficiency was statistically similar among treatment groups. Total viable count and coliform count were significantly lower in the faeces of piglets fed with low protein diets, indicating a reduction in microbial population in faeces of piglets in relation to reduction in dietary protein level. From the overall results, it could be concluded that reducing the dietary protein levels had resulted in reduced growth performance in early weaned piglets, in spite of being supplemented with selected essential amino acids

Preparation and physicochemical characterization of N-succinyl chitosan-coated liposomes for oral delivery of grape seed extract and evaluation of its effect on pulmonary fibrosis induced by bleomycin in rats.

This study aimed to develop an oral succinyl chitosan-coated liposomal formulation containing grape seed extract and assess its therapeutic efficacy in rats with bleomycin-induced pulmonary fibrosis. N-succinyl chitosan was synthesized, and the liposomal formulations were prepared and characterized regarding phenolic content assay and morphology. Size, zeta potential, in vitro drug release, and stability. Pulmonary fibrosis was induced by intratracheal bleomycin injection, and hydroxyproline measurements, lung weight, animal body weight, as well as histopathological studies were performed. Succinyl chitosan increases the physical stability of the formulation, especially in acidic conditions. Drug release studies revealed that 66.27% of the loaded drug was released from CF2 in an acidic medium in 2 hr, but 92.31% of the drug was released in 8 hr in a pH=7 medium. An in vivo study demonstrated that rats exposed to bleomycin significantly lost weight, while those treated with CF2 (400 mg/kg) partially regained weight. Bleomycin treatment increased the mean lung weight and the amount of hydroxyproline in the lungs; these values were significantly decreased in the group treated with 400 mg/kg CF2 (P<0.05). Histopathological examination confirmed that treatment with 400 mg/kg CF2 improved lung fibrosis. In rats, oral administration of N-succinyl chitosan-coated liposomes containing grape seed extract at the 400 mg/kg dose ameliorates bleomycin-induced pulmonary fibrosis.

MARKERS OF INFLAMMATION IN RATS UNDER TOXIC INJURY AGAINST DIETARY PROTEIN DEFICIENCY

The paper presents studies of biomarkers of the development of inflammatory reactions in the blood serum of rats under the conditions of toxic damage with acetaminophen against the background of dietary protein deficiency. The animals consumed a semi-synthetic diet during the experiment according to the recommendations of the American Institute of Nutrition. In order to simulate alimentary protein deprivation, rats received a low-protein diet containing 1/3 of the standard daily protein requirement daily for 28 days. The animals were modeled acute toxic damage with acetaminophen after four weeks of experimental diet. The administration of the toxin was carried out at doses of 1250 mg/kg animal body weight in suspension in 2 % starch gel solution once a day for 2 days by gavage. Determination of the level of C-reactive protein, procalcitonin, tumor necrosis factor-alpha, interleukin-6 in the blood serum of rats was carried out by the method of immunoenzymatic analysis. We have established that toxic damage by the drug xenobiotic - acetaminophen against the background of dietary protein deficiency is accompanied by a maximum increase in the level of C-reactive protein (15.5 times) and procalcitonin (10 times) in the blood serum of rats compared to the control value, which can be considered as prognostic biomarkers of the systemic inflammatory reaction under these experimental conditions. At the same time, under these experimental conditions, hyperproduction of tumor necrosis factor-alpha and interleukin-6 was registered in the blood serum of experimental groups of rats with maximum values when toxic doses of acetaminophen were administered to protein-deficient animals, which is consistent with changes in the level of C-reactive protein and procalcitonin. The fact we found makes it possible to assume that dietary protein deprivation increases the production of TNF-α and IL-6 as pro-inflammatory mediators in toxic liver damage, thus inducing primary damage to liver parenchymal cells..

Characterization of basal seminal traits and semen cryopreservation in Canada lynx (Lynx canadensis)

Little is known about the reproductive biology of the Canada lynx; virtually no data are available describing seminal parameters in this species and sperm cryopreservation studies have not been performed. Our aims were to 1) evaluate effectiveness of two semen collection methods: urethral catheterization (UC) and electroejaculation (EEJ); 2) characterize basal seminal traits throughout the breeding season; 3) compare effectiveness of semen cryopreservation using TEST egg yolk (TEY) or soy lecithin-based (SOY) media; and, 4) evaluate the ability of preserved Canada lynx sperm to fertilize domestic cat in vitro matured oocytes by heterologous in vitro fertilization. Testicular volume averaged 4.5±1.0 cm3. A significant relationship was found between animal body weight and testes volume (P<0.02), as well as for testicular volume and sperm counts per ejaculate (P<0.01). Fecal testosterone concentrations and sperm production were correlated (P<0.01). Electroejaculation was more reliable than UC for sperm collection (8.8 and 1.5 × 106 sperm, respectively; P<0.01). The percentage of sperm with normal morphology was greater in EEJ (29 ± 11 %) than in UC (18 ± 9 %) (P<0.05) samples and primary sperm structural abnormalities were more frequent in UC than EEJ samples (P<0.01). Overall, sperm quality was low in most males throughout the breeding season, but consistent with previous findings in the Lynx genus. Sperm production averaged 10.8 × 106 sperm/ejaculate with 45 % motility; 29 % normal morphology and 69 % acrosome integrity. Motility and acrosome integrity post-thaw declined over time, but were similar between spermatozoa cryopreserved in TEY and SOY media (P > 0.05). Cleavage rates did not differ between TEY (29 ± 17 %) and SOY (27 ± 14 %) and mean numbers of sperm bound to the zona pellucida was similar (20 sperm, TEY vs. 18 sperm, SOY), indicating that both extenders equally preserved the function of Canada lynx sperm for semen banking purposes. Our findings provide zoos and population managers with valuable information about normative reproductive traits in this species, establishing comparative benchmarks for assessing the reproductive potential of specific males recommended for breeding.

Effect of the Lingzi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on Hyperglycemia and Dyslipidemia with Experimental Metabolic Syndrome.

The effect of Ganoderma lucidum hot water extract of submerged cultivated mycelium suspensia on carbohydrate metabolism and lipid profile during fructose-induced metabolic syndrome in rats was studied. The outbred white male Wistar rats, in which metabolic syndrome was induced by consuming a 10% fructose solution instead of drinking water for 42 days, were used. After the induction of metabolic syndrome, the mycelium of G. lucidum in the form of water suspension (a dose of 1 g/kg of the animal's body weight) was administered to animals per os for 7 and 14 days. Glucose concentration was determined using the glucose oxidase method. The content of glycosylated hemoglobin in erythrocytes was determined by the colorimetric method. The concentration of triglycerides, cholesterol, high-density lipoproteins, and low-density lipoproteins in blood plasma was determined by enzymatic methods. A significant decrease in the content of glycosylated hemoglobin was established in animals with metabolic syndrome against the background of administration of the studied suspension. Under the conditions of experimental metabolic syndrome, the administration of mycelium for 7 and 14 days led to a decrease in the concentration of triglycerides by 17.8 and 44.8%, cholesterol by 10.7 and 21.3%, low-density lipoproteins by 14.8 and 28.4%, and to an increase in high-density lipoproteins concentration by 11.9 and 21.5%, compared with metabolic syndrome. The obtained results demonstrate the corrective effect of the suspension of the G. lucidum powdered mycelium on carbohydrate and lipid metabolism, which was directly proportional to the duration of administration.

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.

Bocaiuva (Acrocomia aculeata) nut oil: composition and metabolic impact in an experimental study

This study aimed to obtain physicochemical characteristics and the fatty acid profile of bocaiuva nut oil and to evaluate the impact of its daily consumption on glucose, lipid, and energy metabolism in mice. The acidity content in the bocaiuva nut oil exceeded the maximum limit for crude oils (5.68 mg KOH g-1). However, the peroxide value is within the standard considered adequate for crude oils (3.33 mEq O2 kg-1). In the fatty acid profile, lauric (42.25%) and oleic (23.96%), saturated and monounsaturated, respectively, stand out. After 90 days of in vivo experimentation, the administered oil doses had not influenced the animals' food intake and body weight. Regarding the biochemical parameters, only the non-HDL fraction showed a significant difference, considering that this parameter represents the sum of atherogenic lipoproteins directly linked to atherogenic cholesterol. However, there was no statistical difference between the groups regarding histological changes in the liver, showing that the bocaiuva oil does not cause considerable damage to the liver, even though it is saturated oil. Results show that daily consumption of bocaiuva nut oil did not produce metabolic changes in mice.

ИЗУЧЕНИЕ ДЕЙСТВИЯ КОРМОВОЙ ДОБАВКИ «ФИТОДОК НЕЙРО» НА БЕЛЫХ КРЫС В ХРОНИЧЕСКОМ ЭКСПЕРИМЕНТЕ (сообщение 2)

Feed additives containing biologically active substances are increasingly used to neutralize the negative effects of various toxicants, stress, age-related changes in the brain and to improve the cognitive abilities of animals. The influence of the feed additive «Phytodoc neuro» in doses of 4; 12 and 20 g/kg of feed on the functional state of the liver, kidneys and nervous system, as well as the behavioral responses of white rats in a four-month experiment was studied. Upon receipt of the drug in a therapeutic dose, no negative changes were found on the part of organs and systems important for the body. On the contrary, in the fourth month of the experiment, there was a tendency to increase the body weight and capacity to work of the animals. The body weight of animals fed with the drug at doses of 12 and 20 g/kg, significantly increased at the end of the third month. At a dose of 12 g/kg, starting from the third, at a dose of 20 g/kg after the second and fourth months, muscle strength on the horizontal rod increased, which characterizes the saturation of the body with energy.

DYNAMICS OF MILK PRODUCTIVITY AND BODY WEIGHT OF COWS BY AGE AND PERIODS OF LACTATION

The research was conducted on the farms of the Stepne State Enterprise and the Agroprogres Private Enterprise (stall housing) and on the dairy complex of the Kutuzivka State Enterprise (free housing). It was established that the shape of the lactation curve of first-borns significantly differed from the classical one during untethered confinement. The average daily milk yield reached a maximum at 3-4 months and almost did not decrease until the 7th month of lactation. In older cows, fertility increased and reached a maximum at 2-3 months of lactation, and then gradually decreased. The relative increase in milk yield in comparison with the first month of lactation was 31% in first-born cows, 17% in second-calving cows, 7% in third-calving cows, and 18% in older animals, and in stall housing – 33%, 17%, 10 % and 2 %, respectively. The power of influence (η2) of the month of lactation on the fat content in milk during untethered confinement was 8.5% in first-born cows, 14.5% in the second lactation, 13.1% in the third lactation, 12.2% in older cows, and for tethered confinement 14.8%, 36.9%, 33.6%, and 11.6%, respectively (р&lt;0.001). Similar to the fat content in milk, the protein content of cows also changed during lactation. At the same time, the influence of the month of lactation on this indicator was much smaller than on the fat content, and in some cases it was improbable for stall housing. The influence strength of the month of lactation on the daily yield of cows that were culled from the herd was 23.8% for free housing, 1.9% for body weight, and 8.0% for stall housing and 11.6 % (p&lt;0.001). Correlation coefficients are 0.181, +0.411, and –0.223, +0.335, respectively (p&lt;0.01). Age-related changes in the body weight of animals depended on the technology of their husbandry. In free housing, it was higher both in the sample as a whole (6%) and in animals of different lactations (3-14%). The increase in body weight of cows with age in free housing was: 31 kg in the second lactation, 71 kg in the third lactation, and 100 kg in adult cows, while in stall housing these differences were only 6, 11, 35 kg, respectively. Keywords: husbandry technology, dairy cattle, age, month of lactation, daily yield, fat content, protein content, body weight

Морфологическая характеристика внутренних органов мышей при длительном потреблении микропластика

Introduction.Microplastics (MP) pollute the environment and can pose a danger to living organisms including humans. Experimental studies on mice and rats demonstrated that microplastics can enter the internal environment, causing structural damage to and dysfunction of various organs. However, data on this issue are scarce and contradictory. The aim of this paper was to characterize morphological changes in the internal organs in mice after prolonged MP consumption in different doses. Materials and methods. We formed four groups (n=5 each): three experimental and one control group. Mice of the experimental groups were given a 5-μm polystyrene particle suspension in distilled water at a concentration of 0.1, 1, and 10 mg/l for 4 weeks. The daily consumption doses averaged 0.023, 0.23, and 2.3 mg of microparticles per kg of animal body weight, respectively. The control group received distilled water throughout the experiment. We conducted a morphological examination of the colon, spleen, liver, kidneys, lungs, thymus, mesenteric lymph nodes, brain, heart, testicles, and thigh muscles. In the colon, morphometric methods were used to evaluate inflammatory infiltration, the number of endocrine and goblet cells, and the content of neutral and highly sulfated mucins in the latter. Results. On morphological examination under the influence of 5-μm polystyrene particle consumption in different doses, we revealed pathological changes only in the spleen and colon. However, a decrease in the goblet cell volume fraction in the colon mucosa was found in the group with low dose of microplastics (0.023 mg/kg/day). The group that consumed 2.3 mg/kg/day of microplastics showed the activation of both spleen compartments, an increased endocrine cells count, and a decreased proportion of highly sulfated mucins in goblet cells. Conclusion. Polystyrene microparticles with a 5-μm diameter consumed for 4 weeks at doses of 0.023–2.3 mg/kg/day cause adaptive morphological and functional changes in the colon and spleen. Keywords: microplastics, polystyrene, spleen, colon, internal organs

Lipid-Based Poly(I:C) Adjuvants Strongly Enhance the Immunogenicity of SARS-CoV-2 Receptor-Binding Domain Vaccine

Abstract Background The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly threatened public health. Recent studies have revealed that the spike receptor-binding domain (RBD) of SARS-CoV-2 is a potent target for vaccine development. However, adjuvants are usually required to strengthen the immunogenicity of recombinant antigens. Different types of adjuvants can elicit different immune responses. Methods We developed an RBD recombinant protein vaccine with a polyriboinosinic acid–polyribocytidylic acid [poly(I:C)] adjuvant to evoke a strong immune response. The delivery of poly(I:C) was optimized in two steps. First, poly(I:C) was complexed with a cationic polymer, poly-l-lysine (PLL), to form poly(I:C)–PLL, a polyplex core. Thereafter, it was loaded into five different lipid shells (group II, III-1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC], III-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE], IV-DOPE, and IV-DSPC). We performed an enzyme-linked immunosorbent assay and enzyme-linked immunosorbent spot assay to compare the ability of the five lipopolyplex adjuvants to enhance the immunogenicity of the SARS-CoV-2 RBD protein, including humoral and cellular immune responses. Finally, the adjuvant with the highest immunogenicity was selected to verify the protective immunity of the vaccine through animal challenge experiments. Results Recombinant RBD protein has low immunogenicity. The different adjuvants we developed enhanced the immunogenicity of the RBD protein in different ways. Among the lipopolyplexes, those containing DOPE (III-DOPE and IV-DOPE) elicited RBD-specific immunoglobulin G antibody responses, and adjuvants with four components elicited better RBD-specific immunoglobulin G antibody responses than those containing three components (P &lt; 0.05). The IC50 and IC90 titers indicated that the IV-DOPE lipopolyplex had the greatest neutralization ability, with IC50 titers of 1/117,490. Furthermore, in the challenge study, IV-DOPE lipopolyplex protected mice from SARS-CoV-2 infection. On the fourth day after infection, the average animal body weights were reduced by 18.56% (24.164 ± 0.665 g vs. 19.678 ± 0.455 g) and 0.06% (24.249 ± 0.683 g vs. 24.235 ± 0.681 g) in the MOCK and vaccine groups, respectively. In addition, the relative expression of viral RNA in the vaccinated group was significantly lower than that in the MOCK group (P &lt; 0.05). Interstitial inflammatory cell infiltration was observed in the MOCK group, whereas no obvious damage was observed in the vaccinated group. Conclusions The IV-DOPE–adjuvanted SARS-CoV-2 recombinant RBD protein vaccine efficiently protected mice from SARS-CoV-2 in the animal challenge study. Therefore, IV-DOPE is considered an exceptional adjuvant for SARS-CoV-2 recombinant RBD protein-based vaccines and has the potential to be further developed into a SARS-CoV-2 recombinant RBD protein-based vaccine.

The state of the cardiovascular system of calves in rumen acidosis

Abstract. The purpose of the study is to study the state of the cardiovascular system of calves in scar acidosis. In order to simulate metabolic disorders, crushed barley was injected into the rumen cavity through the fistula at a dose of 10.0-21.0 g/kg of animal body weight, which led to deep biochemical disorders of scar digestion with a pronounced clinical picture of acute rumen acidosis, and after 3.5-4.0 hours - metabolic acidosis. Metabolic acidosis leads to disruption of the functions of all systems, including changes in cardiovascular ac- tivity, which were recorded by clinical examination, electrocardiography, as well as clinical and biochemical blood analysis. As a result, changes in the work of the cardiovascular sys- tem were established, characterized by pronounced ventricular arrhythmia, a decrease in the minute volume of blood ejected by the heart, a violation of the function of automatism, conduction and contractility of the heart muscle.

Paclitaxel Has a Reduced Toxicity Profile in Healthy Rats After Polymeric Micellar Nanoparticle Delivery.

Nanocarrier platforms have been indicated to have great potential in clinical practice to treat non-small cell lung cancer (NSCLC). Our previous Phase III clinical study revealed that polymeric micellar paclitaxel (Pm-Pac) is safe and efficacious in advanced NSCLC patients. However, the histopathological-toxicological profile of Pm-Pac in mammals remains unclear. We examined the Pm-Pac-induced antitumour effect in both A549/H226 cells and A549/H226-derived xenograft tumour models.. And then, we evaluated the short-term and long-term toxicity induced by Pm-Pac in healthy Sprague‒Dawley (SD) rats. The changes in body weight, survival, peripheral neuropathy, haematology, and histopathology were studied in SD rats administered Pm-Pac at different dosages. In the A549-derived xenograft tumour model, better therapeutic efficacy was observed in the Pm-Pac group than in the solvent-based paclitaxel (Sb-Pac) group when an equal dosage of paclitaxel was administered. Toxicity assessments in healthy SD rats indicated that Pm-Pac caused toxicity at an approximately 2- to 3-fold greater dose than Sb-Pac when examining animal body weight, survival, peripheral neuropathy, haematology, and histopathology. Interestingly, based on histopathological examinations, we found that Pm-Pac could significantly decrease the incidences of paclitaxel-induced brain and liver injury but could potentially increase the prevalence of paclitaxel-induced male genital system toxicity. This study introduces the toxicological profile of the engineered nanoparticle Pm-Pac and provides a novel perspective on the Pm-Pac-induced histopathological-toxicological profile in a rat model.