Outbred Rats Research Articles

Study of blood analysis of laboratory animals with subchronic oral toxicity of the drug Amoxiyantar

The article presents the results of studies of subchronic oral toxicity in laboratory animals of the new veterinary drug Amoxiantar. The studies were carried out as part of a laboratory-experimental (preclinical) study of a medicinal product with the aim of introducing it into clinical veterinary practice. Our goal was to study the effect of Amoxiantar on the hematological and biochemical parameters of the blood of laboratory animals. Three experimental groups were formed, of which two experimental and one control, consisting of white outbred rats, 10 animals each. The drug was administered to animals daily intragastrically for 15 days, rats of the first experimental group at a dose of 150 mg/kg body weight, rats of the second group 15 mg/kg body weight, the control group was injected with distilled water. Blood was taken on the first and tenth days after the completion of the administration of the Amoxiantar preparation, on the 16th and 25th day of the experiment, respectively. Statistical processing of the results of the general clinical analysis of the blood of animals on the tenth day after the completion of the drug (25 days of the experiment) revealed monocytosis in the blood of the first and second experimental groups and leukocytosis in the first experimental group compared with the control group, however, these values were normal rat blood parameters. The revealed statistically significant differences, on the 25th day of the experiment, between the second experimental group and the control group in terms of AST, alkaline phosphatase and creatinine were clinically insignificant. During the 25th day of the subchronic experiment, the new veterinary drug Amoxiantar did not adversely affect the hematological and biochemical blood parameters of laboratory animals at doses of 15 and 150 mg/kg of animal body weight.

Changes in the level of endogenous respiration of the small intestine mucosa at various times after irradiation

Objective. To study the level of endogenous respiration of the small intestine mucosa of experimental animals after exposure to external irradiation at a dose of 0.5 and 1.0 Gy.Materials and methods. The study was conducted on white male outbred rats weighing 180-200 g. The animals were irradiated once in the “IGUR-1” unit, 137Cs source, dose rate 0.92 Gy/min. The parameters of tissue respiration were studied by polarographic method using Record-4 device (RF) in a 2 ml cell with a closed platinum Clark electrode at 25°C.Results. It was shown that changes in respiratory activity over time are non-monotonous. This confirms the high sensitivity of the small intestine to radiation exposure.Conclusion. The level of endogenous respiration of the small intestine mucosa can be one of the criteria for assessing the energy status of the tissue after irradiation.

The effect of acetaminophen on the structural and functional state of the large intestine and intestinal microflora

Objective. To assess the condition of the microbial-tissue complex of the large intestine when hepatotoxic concentrations of acetaminophen are administrated to the body of animals.Materials and methods. The experiments were performed on 24 white outbred rats weighing 180–220 g, which were divided into three groups. The control group received 2% starch solution enterally, the first experimental group was enterally administered with acetaminophen in starch solution at a dose of 1500 mg per kilogram of body weight, five times a day with one day interval; and the second experimental group was administered with acetaminophen at a dose of 2500 mg per kilogram of body weight the same way. Free amino acids and their nitrogen-containing metabolites were determined by high-performance liquid chromatography in samples of the microbial-tissue complex (MTC) of the large intestine previously frozen at -70 °C. For microbiological study, the aseptically isolated MTC was immediately sent to a microbiological laboratory for identification of the content of the main representatives of the intestinal microflora. Samples of the wall of the ascending colon were subjected to histological and electron microscopic examination. The hepatotoxic effect of acetaminophen was evaluated by registering the activity of enzymes and the content of total bilirubin in blood plasma.Results. Enteral administration of hepatotoxic amounts of acetaminophen to rats increases the concentrations of free amino acids and their nitrogen-containing derivatives in the microbial-tissue complex of the large intestine. At the same time, the concentrations of essential amino acids are significantly increased. Morphological changes in the cells of the epithelium of the large intestine and the structure of mitochondria have been shown.Conclusions. Toxic doses of acetaminophen have a significant impact on the indicators of the microbial-tissue complex of the large intestine. There are changes in biochemical parameters of amino acid metabolism: increased levels of substitutable amino acids and changes in the colonocytes (size and shape of mitochondria, the height of the brush border, the volume of the goblet cells), indicating decreased ability of the cells to use amino acids to support the functioning of the Krebs cycle. This is also confirmed by significantly increased concentrations of essential amino acids, which are mainly used for protein synthesis. The dysbiosis caused by acetaminophen further contributes to the damage to the large intestine. The negative effect of acetaminophen is confirmed by the dose-dependent changes we found in the microbial-tissue complex.

Changes in social behavior with MAPK2 and KCTD13/CUL3 pathways alterations in two new outbred rat models for the 16p11.2 syndromes with autism spectrum disorders.

Copy number variations (CNVs) of the human 16p11.2 locus are associated with several developmental/neurocognitive syndromes. Particularly, deletion and duplication of this genetic interval are found in patients with autism spectrum disorders, intellectual disability and other psychiatric traits. The high gene density associated with the region and the strong phenotypic variability of incomplete penetrance, make the study of the 16p11.2 syndromes extremely complex. To systematically study the effect of 16p11.2 CNVs and identify candidate genes and molecular mechanisms involved in the pathophysiology, mouse models were generated previously and showed learning and memory, and to some extent social deficits. To go further in understanding the social deficits caused by 16p11.2 syndromes, we engineered deletion and duplication of the homologous region to the human 16p11.2 genetic interval in two rat outbred strains, Sprague Dawley (SD) and Long Evans (LE). The 16p11.2 rat models displayed convergent defects in social behavior and in the novel object test in male carriers from both genetic backgrounds. Interestingly major pathways affecting MAPK1 and CUL3 were found altered in the rat 16p11.2 models with additional changes in males compared to females. Altogether, the consequences of the 16p11.2 genetic region dosage on social behavior are now found in three different species: humans, mice and rats. In addition, the rat models pointed to sexual dimorphism with lower severity of phenotypes in rat females compared to male mutants. This phenomenon is also observed in humans. We are convinced that the two rat models will be key to further investigating social behavior and understanding the brain mechanisms and specific brain regions that are key to controlling social behavior.

Comparative Preclinical Evaluation of the Safety, Antifungal Activity, and Pharmacokinetics of Sertaconazole Products for External Use

SCIENTIFIC RELEVANCE. The high prevalence of fungal skin infections motivates expanding the range of sertaconazole products for external use.AIM. The study was a preclinical comparison of the safety, antifungal activity, and pharmacokinetics of Sertaverin® 2% medicated shampoo (VERTEX JSC, Russia) with those of Sertamicol® 2% solution for external use (Glenmark Pharmaceuticals Ltd, India) and Nizoral® 2% shampoo (Janssen Pharmaceuticals N.V., Belgium) approved in the Russian Federation.MATERIALS AND METHODS. In the toxicity study, the medicinal products were applied to the skin of male and female outbred rats at doses of 0.5 or 1.5 mL/animal for 28 days. The authors evaluated the pharmacokinetics of two sertaconazole formulations (shampoo and solution) following a single administration to adult male rats at the same dose. Nizoral® was not used in the pharmacokinetics study because it contains a different active substance, ketoconazole. The minimum inhibitory concentration (MIC) was determined using the serial microdilution method in a wide range of concentrations.RESULTS. The medicinal products did not exhibit any significant toxic effects in laboratory animals after 28 days of repeated dermal application. Plasma sertaconazole concentrations were negligible. Sertaconazole was intensively distributed in the liver, which is a highly vascularised organ, and in the target organ (skin at the site of application). The relative bioavailability of sertaconazole from the shampoo relative to that from the solution for external use was approximately 30% in liver tissues and approximately 363% in skin tissues at the application site. Sertaverin® was comparable to sertaconazole in the active substance form in terms of inhibiting the growth of Malassezia furfur strains. The MICs calculated on the active substance basis were ≤16–64 μg/mL.CONCLUSIONS. With its synergistic dual mechanism of action, broad-spectrum antifungal activity, lipophilic properties, and low systemic absorption, Sertaverin® may provide a more effective and safe alternative to marketed medicinal products for scalp diseases.

Cocaine Regulates NLRP3 Inflammasome Activity and CRF Signaling in a Region- and Sex-Dependent Manner in Rat Brain.

Cocaine, one of the most abused drugs worldwide, is capable of activating microglia in vitro and in vivo. Several neuroimmune pathways have been suggested to play roles in cocaine-mediated microglial activation. Previous work showed that cocaine activates microglia in a region-specific manner in the brains of self-administered mice. To further characterize the effects of cocaine on microglia and neuroimmune signaling in vivo, we utilized the brains from both sexes of outbred rats with cocaine self-administration to explore the activation status of microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activity, corticotropin-releasing factor (CRF) signaling, and NF-κB levels in the striatum and hippocampus (HP). Age-matched rats of the same sex (drug naïve) served as controls. Our results showed that cocaine increased neuroinflammation in the striatum and HP of both sexes with a relatively higher increases in male brains. In the striatum, cocaine upregulated NLRP3 inflammasome activity and CRF levels in males but not in females. In contrast, cocaine increased NLRP3 inflammasome activity in the HP of females but not in males, and no effects on CRF signaling were observed in this region of either sex. Interestingly, cocaine increased NF-κB levels in the striatum and HP with no sex difference. Taken together, our results provide evidence that cocaine can exert region- and sex-specific differences in neuroimmune signaling in the brain. Targeting neuroimmune signaling has been suggested as possible treatment for cocaine use disorders (CUDs). Our current results indicate that sex should be taken into consideration when determining the efficacy of these new therapeutic approaches.

Ektacytometry: characterization of the erythrocytes of rats subjected to hypothermia and receiving natural zeolites

The article presents data as to the effect of a diet containing natural zeolite, taken from the Mysovsky mine (Khanty-Mansi Autonomous Okrug - Ugra), and applied in powdered form on the ability of erythrocytes of white outbred rats to change their shape in shear flow under normal and hypothermic conditions. To assess the deformability of erythrocytes, a laser diffraction technique combined with a redesigned version of the ektacytomer has been used in this work. For comparison, zeolite from the Kholinsky mine (Zabaykalsky Krai), which is well-studied and widely used for medicines and nutraceuticals has been provided. It has been shown that hypothermia causes a significant increase in the parameter such as erythrocyte deformability in rats in a cold group and is associated with enhanced lipid peroxidation when compared to animals in a control group. These alterations were a result of macrocytosis, revealed by flow cytometry analysis. Natural zeolite powder used in animal feeds had antioxidant and membrane-protective effects on animals in both groups. These included a significant increase in the parameter such as erythrocyte deformability with a decrease in lipid peroxidation processes and expansion of the Price-Jones curve to the left, unlike those observed in animals subjected to hypothermia but not receiving zeolites. The results obtained demonstrated that the biological effects of natural zeolite-containing preparation which contains a clinoptilolite component are similar and that zeolites from the Mysovsky mine can be used as a potent raw material for drugs.

Аnalysis of the influence of basic acrylic plastics "Ftoraks" and "Villacryl H Plus" on the main hematological parameters in the experiment

Summary. The effectiveness of orthopedic treatment significantly depends on the properties of the basic plastics used in the manufacture of dentures.
 The aim of the study – to study the effect of acrylic plastics "Ftoraks" and "Villacryl H Plus", the polymerization of which was carried out by different methods, on the main hematological parameters.
 Materials and Methods. The study and comparative characterization of the possible toxic effects of dental base acrylic plastics "Ftoraks" and "Villacryl H Plus", which were polymerized by different methods, on the main hematological parameters were performed on white outbred rats, which implanted samples of these materials in periodontal tissue.
 Results and Discussion. As a result of the study, it was found that animals implanted with samples of the above acrylic plastics polymerized in a "water bath" methodic in the blood had a decrease of hemoglobin, leukocytosis, increased number of band and segment nuclear neutrophils, increase in the number of eosinophils and decrease of basophils in comparison with the control and other groups of animals. In the study of samples polymerized in the apparatus for dry polymerization under pressure and in the apparatus for molding plastics, it was found that fluctuations in the content of the main hematological parameters are within the physiological norm and do not differ significantly from the control.
 Сonclusions. Dental basic acrylic plastics "Ftoraks" and "Villacryl H Plus" polymerization of which was carried out by the method of dry polymerization with pressure and in the apparatus for foundry pressing of plastics cause less toxic effects on hematological parameters of the blood.
 
 

Alcohol, place conditioning, and male rats: A systematic review for outcome prediction.

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). To predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. Systematic review: structured search for relevant records in PUBMED and two other sources, eligible articles defined as those conforming to all inclusion criteria, selection of experiments failing all the exclusion criteria, and analysis of procedure-outcome relations according to the background of variables affecting associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre-exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict different rates of CPA and CPP: higher rates of CPA are predicted by single-housed, older, and heavier animals, while higher rates of CPP are predicted by group-housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, indicate the predictive analysis has broad consequences (from theoretical to translational ones) for PC in alcohol research, and specify variables needing more accurate investigation (rat sex, age, weight, strain, spatial configuration of the apparatus, and conditioning timetable). This review may improve our comprehension of results of alcohol-induced PC with rats, refining our understanding of the motivator function of alcohol and the alcohol-seeking behavior triggered by environmental contexts, and opening new research venues on their neurobiological basis.

Histochemical changes in the tooth and jaw germs of laboratory rats under the influence of ecotoxicants and during perinatal prevention

Relevance. Unreasonably high pollutant emissions into the environment, the ill-considered use of natural resources and the raw material orientation of exports have led to an environmental crisis in many areas.Purpose. To study the effect of ecotoxicants on the histochemical structure of tooth and jaw germs in laboratory rats and ways to reduce this effect during perinatal prevention.Materials and methods. The experiment included 50 white outbred rats weighing 180-250 grams. All animals formed five groups: 1 control and four experimental. All animals of the experimental groups were subject to gasoline and formaldehyde vapours inhalation exposure; Group 1 (control) was subject to only poisoning with ecotoxicants, Group 2 had peptinsorbent associated with ecotoxicant poisoning, Group 3 – a membrane protector – magnolia vine, Group 4 – beet, Group 5 – peptinsorbent, membrane protector and beet.Results. The histochemical study of tissues around the tooth germs in pup rats born from the control group rats after poisoning with ecotoxicants revealed an increased mast cell number in the tissues compared to intact rats. The samples of Group 2 rats showed that the mast cell number and characteristics practically did not differ from the control group after ecotoxicant poisoning. In the rats of Group 3, the number of mast cells was slightly lower than in the control group. In Group 4, the number of mast cells was not significantly lower than in the control group. In the rats of Group 5, the number of mast cells significantly decreased compared to the control and other experimental groups.Conclusion. Thus, during subchronic poisoning of pregnant female rats with ecotoxicants, the number of mast cells in the gingiva of rat pups increases against the background of microcirculation disorders. The number of mast cells in gingiva significantly decreases and approaches the normal values in rat pups after feeding pregnant rats with the combined mixture (peptinsorbent+membrane protector Schisandra+beetroot).

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

Aims: to study the content of regulatory peptides in the hypothalamus and pituitary gland, as well as sex steroids in the gonads in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. Our experiment was performed in white outbred rats of both sexes with induced hypothyroidism, against the background of which Guerin’s carcinoma was transplanted. In 1% homogenates of the pituitary and the hypothalamus and in 10% homogenates of the gonads in the animals from the main and reference groups, the levels of GnRH (Casabio, China) were determined by the ELISA method using standard kits, and the content of LH, FSH, estradiol (E2), testosterone (T) and progesterone (P4) by the RIA method (Immunotech, Czech Republic). Statistical analysis of the results was performed using the Statistica 10.0 software package. Results. In females of the main group, the level of GnRH in the hypothalamus increased by 1.6 times, but the content of LH and FSH in the pituitary gland decreased, while in males the content of GnRH decreased by 1.4 times and FSH by 1.6 times compared with the intact animals. In the gonads of females of the main group, the content of E2 and T decreased by 1.3 times, but the level of P4 increased by 4.7 times, while in males the T production decreased by 7.1 times. Hypothyroidism, against the background of which Guerin’s carcinoma developed, had a significant effect both on the central links of the HPG axis and the peripheral ones, producing an additional hormonal imbalance in sex steroids

Changes in the functional activity of the hypothalamic-pituitaryadrenal axis in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism

The hypothalamic-pituitary-adrenal axis (HPA) makes the body’s response to various stress factors, interacting with the thyroid and gonadal axis. The aim of our work was to study the effect by induced hypothyroidism on changes in the functioning of the HPA axis in rats with Guerin’s carcinoma of both sexes. Materials and methods. The experiment was performed in white outbred rats of both sexes. Hypothyroidism was induced in animals by medication for 30 days with Mercazolil, and then Guerin’s carcinoma was transplanted (the main group). The reference groups covered animals with the independent growth of Guerin’s carcinoma and with independent hypothyroidism, as well as intact animals (the normal conditions). On day 18 of the tumor growth, the animals were sacrificed, and, using standard ELISA kits, in the serum and the homogenates of the adrenal glands, the tumor and the perifocal zone, the level of cortisol was determined; in the homogenates of the hypothalamus we measured the concentration of CT-releasing hormone (CRH) and in the pituitary gland the concentration of ACTH. Results. Induced hypothyroidism both in males and females caused adrenal insufficiency. The growth of Guerin’s carcinoma increased the level of CT-releasing hormone in males by 9.6 times and cortisol in the adrenal glands in females and males by 1.3 times and 2.3 times (p<0.05), respectively. In the main group females and males we revealed a decrease in the level of CT-releasing hormone of the hypothalamus by an average of 1.4 times, ACTH in the pituitary gland by 1.5-1.8 times, but an increase in the cortisol concentration in blood and the adrenal glands only in males by an average of 1.5 times (p˂0.05). Only in males of the main group in the tumor and its perifocal zone, the content of cortisol increased by 5.9 times and 1.6 times (р˂0.05), respectively. Conclusion. The HPA axis has a gender-specific response to the growth of a malignant tumor, both in its independent growth variant and against the background of hypothyroidism, which in its independent variant causes adrenal insufficiency.

Novel 1,4-Dihydropyridine Derivatives as Potential Agents with Analgesic Activity IN Orofacial Trigeminal Pain Test: Experimental Preclinical Randomized Trial

Background. In the majority of cases, contemporary pharmacological correction mainly focuses on the most effective analgesia. Therefore, the search for and research into new analgesic drugs are a priority in modern pharmacology.Objective — to establish the level of analgesic activity in eight novel heterocyclic compounds of 1,4-dihydropyridine derivatives synthesized in a classic test of orofacial trigeminal pain in animal experiments.Methods. An experimental preclinical randomized trial of the analgesic activity in 1,4-dihydropyridine derivatives was carried out. The experiment was conducted on 100 white male outbred rats in the laboratory of the Fundamental and Clinical Pharmacology Department, St. Luke Lugansk State Medical University, Lugansk People’s Republic. Novel 1,4-dihydropyridine derivatives were preliminarily investigated in a virtual biological screening by means of Swiss Target Prediction tool (Swiss Institute of Bioinformatics, Switzerland). The laboratory animals were divided into a control group (rats were exposed to acute pain syndrome by injecting 0.1 ml of 5% formalin solution into the vibrissae area without pharmacological correction), a comparison group (rats which received metamizole sodium (OOO Farmstandard) at a dose of 7 mg/kg 1.5 hour prior to acute pain syndrome modeling in the vibrissae area), and eight experimental groups (1.5 hours before formalin administration, novel 1,4-dihydropyridine derivatives under study at a dose of 5 mg/ kg were intragastrically injected). 10, 15 and 20 minutes after simulating acute pain, the number of scratching movements of the forelegs around orofacial region per minute was counted. Statistical processing of the results involved methods of mathematical statistics for quantitative variability and was carried out using Statistica 12.5 (IBM, USA).Results. Animals treated with 1,4-dihydropyridine derivatives d02-133 and d02-172 under the experimental conditions showed a significant (13–21 times) decrease in scratching movements frequency by the 10th minute of observation in comparison with the control group. By 15th minute, the analgesic activity of the cyanothioacetamide derivatives increased 14 and 11 times as compared to these indicators of the reference group. After 20 minutes, the analgesic activity of these compounds in terms of inhibiting nociceptive impulses, as compared to the control group, was also high, as the number of scratching movements in the vibrissae area in animals of these experimental groups was 8–9 times lower than in control group. The orofacial trigeminal pain test detected the most exhibited analgesic activity in novel cyanothioacetamide derivatives d02-139, d02-133, and d02-172, which appeared to be higher than that of metamizole sodium.Conclusion. It was found that novel original derivatives of 1,4-dihydropyridine showed a high degree of analgesic activity.

Effect of mesenchymal stem cell transplantation on the structural and functional parameters of the liver in acute toxic hepatitis in rats

Acute toxic hepatitis is a serious health problem for the working population. The currently widely used pharmacological preparations with claimed hepatoprotective properties for the treatment of liver diseases have dubious therapeutic efficacy and cannot restore functional and structural changes in the damaged organ. Thus, the search for new methods of treating liver diseases, including toxic etiology, is an urgent task. An experimental study was conducted on 134 nonlinear white outbred rats (35 months) weighing 250390 g. The animals were divided into four groups: group I, control group (n = 15); group II, single intragastric administration of an oil solution of carbon tetrachloride at a dose of 1500 mg/kg (n = 41); group III, single intravenous administration of multipotent mesenchymal stem cells of the mouse (n = 20); group IV, single intragastric administration of an oil solution of carbon tetrachloride at a dose of 1500 mg/kg and subsequent intravenous transplantation of multipotent mesenchymal stem cells of the mouse (2 106) (n = 58). On days 1, 3, 5, and 7 of the experiment, blood sampling was performed for biochemical analysis, and organs and tissues were selected for histological and morphometric studies. The transplantation of multipotent mouse mesenchymal stem cells reduced the mortality of animals after exposure to carbon tetrachloride and did not cause acute toxicity. According to a morphometric study, starting from day 3, the introduction of multipotent mouse mesenchymal stem cells led to a statistically significant decrease in the infiltrative processes in the liver tissue. Statistically significant changes in the biochemical composition of the rat blood serum were noted against the transplantation of multipotent mouse mesenchymal stem cells: a decrease in the activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase, amylase, creatinine, uric acid, direct and total bilirubin, and cholesterol. The transplantation of multipotent mouse mesenchymal stem cells was found to be an effective method of treating acute toxic hepatitis. The use of multipotent mouse mesenchymal stem cells contributed to an increase in the survival rate of laboratory animals and faster recovery of structural and functional disorders in liver tissue after its acute toxic damage.

ВЛИЯНИЕ МАСЛА СЕМЯН ТЫКВЫ НА СКОРОСТЬ ПОТРЕБЛЕНИЯ КИСЛОРОДА ТКАНЬЮ ПРОСТАТЫ

Despite a long and successful experience with the use of pumpkin seed oil (PSO) in patients with chronic prostatitis (CP), the pharmacodynamics of PSO is not fully understood. We hypothesized that pumpkin seeds and PSO contain pharmacologically active substances that are able to influence on the rate of oxygen consumption (ROC) by the prostate tissue, which may be a determinant of their effectiveness in men with CP. The aim: to study the effect of eating pumpkin seeds, containing PSO, on the ROC of the prostate tissue in white outbred rats. Materials and methods. The control group consisted of 16 outbred male rats. The experimental group consisted of 6 white outbred male rats, which on the eve received, in addition to the standard diet, pumpkin seeds without restriction. Thus, 22 adult outbred male rats were used in the study. The ROC of the prostate tissue was measured by an optical sensor of dissolved oxygen with a DKTP-03 thermoelectric converter. A prostatectomy was performed under anesthesia. Immediately after that, prostate tissue weighing 0.5 g was placed in a beaker, filled with 15.0 ml of 0.9% sodium chloride solution at a temperature of 36.6 °C. An optical oxygen sensor DKTP-03 connected to an oxygen analyzer "Expert-009" was placed in a beaker and the tightness was created. The analyzer showed the concentration of dissolved molecular oxygen (CDO2) in a 0.9% solution of sodium chloride, expressed in mg / l. We recorded the CDO2 readings every minute from the beginning of the experiments (0 minutes) to their end (60 minutes). Results and conclusion. we have found for the first time that PSO statistically significantly increases the ROC in rat prostate tissue (p < 0.05).

Influence of high-bromine poultry products on clinical-biochemical blood parameters of white rats

Bromine content in fodder and water for laying chickens in Ukraine gradually increasing, thereby accumulating in the poultry production (eggs and meat): according to the data, intake of bromine with chicken eggs in 2020 has almost doubled, compared with 2016. Taking into account the ability of bromine to accumulate and the scales of consumption of poultry products, it is relevant to study the effects of high bromine concentration on the level of thyroid hormones and clinical-biochemical parameters of blood of white rats. At the laboratory of Toxicological Monitoring of the National Scientific Center the Institute of Experimental and Clinical Veterinary Medicine and the Department of Experimental Pharmacology and Toxicology of the State Institution V.Y. Danylevskyi Institute of Problems of Endocrine Pathology of the National Academy of Medical Sciences of Ukraine, we carried out studies on white outbred male rats (n = 144). The diet of experimental groups was supplemented with eggs and meat containing high bromine concentration. We determined increase in the coefficients of liver weight and decrease in the coefficients of lung weight in the experimental rats. Moreover, we determined changes in the biochemical blood profile, in particular: after egg consumption, there occurred 20.0–22.0% decrease in the enzymatic activity of alanine aminotransferase, 23.0–48.4% in the activity of aspartate aminotransferase, and on average 21.3% decrease in alkaline phosphatase, compared with the control; after meat consumption, the level of total proteins decreased by 8.6%, glucose by 12.2–14.5%, also there were 13.8–18.5% decrease in the activity of alanine aminotransferase and 12.1–83.0% increase in the activity of aspartate aminotransferase on the 28th day, and 23.2–35.3% decrease in the activity of alkaline phosphatase. After the intake of both poultry products, the blood serum of animals was observed to have decrease in the level of overall thyroxine and overall triiodothyronine (1.3 times on average, depending on the period of study). The results of the studies can help in prediction and timely alleviation of the negative impact of poultry products with high bromine content on the human organism.

Changes in the parameters of pro-oxidant–antioxidant balance in the brain of rats with stepwise incomplete cerebral ischemia

Objective: to evaluate the activity of oxidative stress in rats with stepwise incomplete cerebral ischemia (SICI). Material and methods. Experiments were performed on 24 male outbred rats weighing 260±20 g, allocated into 3 subgroups (6 animals in each) based on time of ligation of both common carotid arteries (CCA). The control group comprised of sham-operated rats of the same sex and similar weights (n=6). To identify the pro-oxidant–antioxidant state of the brain based on its homogenates, the activity of lipid peroxidation processes, the content of thiobarbituric acid reactive substances (TBARS), the concentration of reduced glutathione (GSH), total thiol groups (TSH), and the activity of glutathione peroxidase were determined. Results. SICI with ligation interval of both CCAs of 1 day and 3 days led to a significant decrease in the total SH groups of proteins and glutathione by 30% (p=0.038) and 46% (p=0.044), respectively, TBARS concentration by 29% (p=0.038) and 31% (p=0.043), respectively. SICI with the maximum interval between CCA ligations was manifested by less pronounced changes in the pro-oxidant–antioxidant state of the brain. Conclusion. In SICI with ligation of both CCAs 7 days apart, at which histological changes were the least pronounced, changes in the pro-oxidant–antioxidant balance were insignificant. The most pronounced disorders of the pro-oxidant–antioxidant balance in the brain were observed in the subgroup with the minimum interval between CCA ligations, which implied the highest activity of oxidative stress.

Cytotoxicity and Antitumor Activity of Arglabin and its Derivatives.

At present, more than 8000 sesquiterpene lactones have been isolated and described from natural sources, a significant part of which has cytotoxicity and antitumor activity. One of the practically available sesquiterpene lactones is arglabin, which, as a renewable material, is used for the synthesis of new compounds. The article presents data on the study of cytotoxicity and antitumor activity of the arglabin and its derivatives using molecular modeling methods and, in the experiment in vitro and in vivo. The aim of this work is to study the cytotoxicity and antitumor activity of new compounds based on the sesquiterpene lactone arglabin using molecular modeling and experimental pharmacology. ChemDraw programs and a set of AutoDock programs were used for computer simulation. Molecular docking was carried out using the Maestro graphical interface of the Schrödinger Suite software package (Schrödinger, LLC, New York, NY, 2017). Docking modes standard precision and XP (extra precision) were used. In in vitro experiments, the antitumor activity of compound samples was studied in models of 60 human tumor cell lines, and clonogenic C6 rat glioma cells. The antitumor activity of the samples was studied in experiments in vivo on white outbred rats with transplanted tumors and was evaluated by the inhibition of tumor growth and the magnitude of the increase in average life expectancy. When studying the antitumor activity on 60 cell lines of tumor cells (NCI60), clonogenic cells of C6 rat glioma, a high antitumor activity of some arglabin derivatives was established. The connection between the structure of arglabin derivatives and their inhibitory effect on farnesyl protein transferase, topoisomerases -I and -II was studied.

ВЛИЯНИЕ ЭКОТОКСИКАНТОВ НА ЗАЧАТКИ ЗУБОВ ЛАБОРАТОРНЫХ ЖИВОТНЫХ

More than 75% of waste is toxic to the environment and humans. The aim of the study was to invistigate the toxic effect of ecotoxicants on the rudiments of the teeth of laboratory animals. The experiment was carried out on 30 white outbred rats weighing 180–250. All animals were divided into 2 groups: control (Group 1) and experimental (Group 2). During the experiment, all animals of the experimental groups were subjected to inhalation exposure to gasoline and formaldehyde vapors. Animals of the control group were supplied with normal air around the clock. The jaws of rats were decalcified for 30 days in a 10% formic acid solution in a 10% buffered formalin solution. After dehydration of the material in a battery of alcohols of increasing concentration (ethanol - concentration from 70% to 100% absolute) was poured into paraffin according to the generally accepted method. Using a rotary microtome brand LEICA RM 2145 (LEICA, Germany), histological sections 5–8 µm thick were made. The sections were stained with hematoxylin and eosin and picrofuchsin according to the Van Gieson method. Stained sections were examined and photographed using an AXIO IMAGER-Z1 light microscope (CARL ZEISS, Germany). In the control group of rats, a morphological picture of normal tooth histogenesis was observed at a late stage of development. In the structure of the tooth germs of rat pups of the 2nd group, a violation of the processes of histogenesis of most tooth germs and a change in the structure of the periodontal tissues were found. In the epithelium of the gingival mucosa, signs of dystrophic changes were determined, up to cell destruction; in the connective tissue plate of the gingival mucosa, in the periodontium and in the zone of formation of the alveolar bone, signs of inflammatory phenomena were determined in the form of cell infiltrations and circulatory disorders in the form of expansion of the lumens and blood filling of the vessels. In the area of the tooth germs, destructive changes in odontoblasts and enameloblasts were manifested, which was probably one of the reasons for the disruption of the processes of dentinogenesis and enamel formation, expressed in the heterogeneity of the formation of dentin and enamel layers. This confirms the toxic effect of ecotoxicants on the rudiments of the teeth of laboratory animals.

INTEGRATIVE AND BIOCHEMICAL PARAMETERS IN RATS IN THE SIMULATION OF DOXORUBICIN CHRONIC HEART FAILURE AND DURING THE USE OF Β-ADRENERGIC BLOCKERS

β-adrenergic blockers have been actively used in the treatment of heart failure, which relieve excessive sympathetic stimulation of the myocardium, reduce calcium overload of cardiomyocytes, reduce the heart's oxygen demand, inhibit lipid peroxidation and stabilize cell membranes, have an antiarrhythmic effect. The aim: to compare efficiency of various drugs with new potential "Hypertril" in the conditions of modeling doxorubicin chronic heart failure (CHF) to improve parameters. Objective: CHF was modeled on 85 white outbred rats weighing 190–220g by administering doxorubicin at a cumulative dose of 15 mg/kg. Material and metods: Nebivalol, Carvedilol, Bisoprolol, Metoprolol and Hypertril were administered intragastrically once a day in the form of a suspension of 1% starch mucus for 30 days after a 14-day administration of doxorubicin. To determine damage, we used the solid-phase immunosorbent sandwich ELISA method, enzyme immunoassay and the immunoturbodimetric method. Result and discussion: Administration of Hypertril to rats with CHF led to a decrease in the blood of the main molecular markers of CHF to the values of intact animals, which indicated its significant cardioprotective effect in comparison with other drugs. Hypertril reduces manifestations of mitochondrial dysfunction, protects the myocardium and positively affects the morphological and functional parameters of cardiomyocytes, inhibits apoptosis