White Mice Research Articles

Influence of Okra Extract Supplementation on Some Haematological Parameters of Male Mice Exposed to Aflatoxin

This research was directed to determine the influence of an alcoholic extract of okra on the lessening of the destructive impact of the aflatoxin produced by Aspergillus fumigatus in white mice and its influence on some physiological blood parameters. Different food samples, (grains and fruits) such as (wheat, barley, corn, rice, citrus, strawberries, and apples) were selected for the isolation of a variety of fungi. The results showed that Aspergillus flavus 15(18.7%), Aspergillus niger12(15%), Penicillium spp 7(8.7%), Aspergillus terreus 7 (8.7%), Aspergillus fumigatus7(8.7%), Alternaria spp. 10 (12.5%), Aspergillus parasiticus 6 (7.5%) Fusarium 6 (7.5%), Penicillium chrysogenum5(6.3), Mucor spp.2(2.5%),and Rhizopus stoloinfier 3(5.5%).The identified fungi were tested for aflatoxin production, and the results revealed that Aspergillus fumigatus produced the most aflatoxin. Okra alcoholic extract was tested in vivo against the negative impact of aflatoxins using different concentrations. The findings revealed that alcoholic extracts showed reasonable influence on some blood parameters, and the results are promising.

Microbiological characteristics and antibiotic sensitivity of <i>Mycobacterium avium</i> subsp. <i>paratuberculosis (MAP)</i> isolated on the territory of Western Siberia

The results of the studies of microbiological features of cultures of standardized and clinical strains isolated from biological material of the animals on the territory of Western Siberia belonging to Mycobacterium avium subsp. paratuberculosis (MAP) are presented. Microbiological studies of the pathogens consisted of the bacterioscopic method (staining of smears of cultures according to Ziehl – Neelsen) and the culture method (processing of biomaterial by the method of A.P. Alikaeva with subsequent sowing of the obtained sediment on Lowenstein-Jensen and Finn-2 egg nutrient media with mycobactin). In addition, biochemical tests with the cultures isolated from the material were used, including examination of colony growth at 30, 37 and 42 C, on the medium with sodium salicylate, with 5% sodium chloride, nitrate reduction, determination of amidase, catalase, arylsulfatase activity, hydrolysis of Tween-80 and a biological method consisting of intravenous infection with suspensions of standardized and clinical strains of non-linear white mice. The results of the studies showed that the cultures of clinical strains belonged to the 3rd group of mycobacteria according to the Runyon classification and their properties were identical to the standardized strain of M. paratuberculosis, which allows us to attribute them to mycobacteria of paratuberculosis. Antibiotic sensitivity studies of the standardized strain of M. paratuberculosis (Central-Lubinsky) and clinical strains revealed their susceptibility to all the drugs used in the studies. In a biological assay, mice infected with paratuberculosis pathogens had lower body weight than in the control groups. Autopsy revealed enlargement of lungs, spleen and liver, single purulent foci on liver, spleen and mesentery, and the liver was marbled, the mucosa of the small intestine is not changed. The growth intensity of cultures from the biomaterial (lungs, liver, spleen) was 2(++) to 3(+++) to 4(++++) points, the growth intensity of the cultures from the mucosa of the small intestine is 0(+/-) points. Bacterioscopic examination of smears of colony cultures of the studied pathogens isolated from the internal organs of mice of the experimental groups and stained by Ziehl – Neelsen staining showed the presence of single acid-fast granular bacilli arranged in groups or in the form of a "palisade", which is characteristic of the causative agent of paratuberculosis. The biological method of research on laboratory animals revealed the susceptibility of nonlinear white mice to the tested cultures and the possibility of reproducing experimental paratuberculosis infection on them.

EFFECT OF HUMIC FEED ADDITIVE ON METABOLIC PROCESSES AND PRODUCTIVITY OF BEEF CATTLE

The use of made in Kazakhstan organic and mineral feed additives to in-crease the meat productivity of cattle is important for the agro-industrial complex of the Republic. During the study, qualitative and quantitative analysis of raw materials was made. Quality control of the finished feed additive was carried out following the requirements of the State Pharmacopoeia of the Republic of Kazakhstan. The studies were conducted in accordance with the requirements of the Technical Regulations approved by the Decree of the Government of the Republic of Kazakhstan dated April 23, 2008 No. 380, Regulation No. 7-1/625 dated 11/28/2014 and Regulation (EC) No. 1831/2003 of the European Parliament and of the Council of September 22, 2003, on additives for use in animal feeding. Kazakh potassium humate of the Maykubensky deposit is sterile, non-pyrogenic, non-toxic, and harmless, with an average pH of 11.0-1.0, and has a biological effect on laboratory animals (white mice). The effectiveness analysis in the production experiment allowed us to identify the positive effect of feed additives on metabolic processes and increasing meat productivity in bulls. Regardless of age, on the 7th day of taking the feed additive of potassium humate, the calves' coats acquired a noticeable shine and a bright color, and shedding was completed with-in a month. Clinical signs of metabolic disorders and vitamin deficiency, detected in the farm at the time of the experiment in some animals, pass through 20-30 days from the beginning of the application of the feed additive. The optimal scheme for the use of feed additives was tested on the Kazakh meat breed Akbas, and the concentration of humic substances was selected for the maximum mani-festation of the biologically active effect. Animals became mobile and active, their rumination became more active, they grew noticeably, and the average daily weight gain increased by 7.6-8.9%.

ANALGESIC POWER OF THE INSOLUBLE FRACTION N-HEXANE OF MELINJO LEAVES (Gnetum gnemon L.) IN SWISS MICE (Mus musculus)

Melinjo (Gnetum gnemon L.) contains various secondary metabolites, including alkaloids, flavonoids, saponins, and tannins. Flavonoids function as analgesics and inhibit cyclooxygenase enzymes, which reduce prostaglandin production and pain. This study aimed to determine the analgesic power of the n-hexane-insoluble fraction of melinjo leaves (Gnetum gnemon L.) as an effective analgesic in male white mice (Mus musculus) and to determine the most effective analgesic dose. This research was conducted using test animals of 25 male white mice (Mus musculus) divided into 5 groups, each consisting of 5 mice. The negative control group (Na-CMC) was 0.5%, the positive control group received a mefenamic acid dose of 65 kg/BW, and the insoluble fraction hexane group (ifh) received doses of 50 mg/kg BW, 100 mg/kg BW, and 200 mg/kg BW. The chemical stimulus was administered at a dose of 400 mg/kg body weight acetic acid. The number of wriggles in male white mice (Mus musculus) was measured every 10 minutes for 60 minutes. The results of the study showed a significant difference between the negative control (Na-CMC 0.5%) and various doses of insoluble fraction hexane groups, while the positive control (mefenamic acid 65 mg/kg BB) showed no difference with ifh doses of 100 mg/kg BB and 200 mg/kg BB ...

Study of the Anti-inflammatory Activity of 2-hydroxy-4-oxo-4-R-2-butenoates of Heterylammonium, which Have an Effect on the Blood Clotting System

Introduction. The use of anticoagulants is relevant in therapeutic, cardiological, neurological practice, geriatrics, obstetrics and gynecology, as well as in complications associated with COVID-19 infection and vaccination. In-depth studies of additional pleiotropic effects of existing anticoagulants are being conducted. The anti-inflammatory effect of heparins and direct oral anticoagulants was found. Special emphasis is placed on the existing close relationship between coagulation and inflammatory processes. The interaction of anticoagulants with nonsteroidal anti-inflammatory drugs when taken together is actively discussed. The combination of anticoagulant and anti-inflammatory action in one chemical molecule can solve the problem of polypragmasia.Aim. To study the anti-inflammatory activity of promising 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system.Materials and methods. For further study of anti-inflammatory activity, 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium, which have an effect on the blood clotting system, were selected. The anti-inflammatory effect was studied on a model of acute inflammatory edema in mongrel rats of both sexes weighing 180–250 g. The studied compounds were administered intragastrically. Diclofenac sodium and nimesulide substances administered similarly were used as comparison drugs. Acute toxicity of substances that showed activity was studied on white nonlinear mice of both sexes weighing 18–22 g with the definition of LD50.Results and discussion. All the studied 2-hydroxy-4-oxo-4-R-2-butenoates of heterylammonium have anti-inflammatory effects of varying severity. Data on the study of acute toxicity during intragastric administration, allow us to attribute the studied compounds to the 4.5 class of the hazard classification of chemical products.Conclusion. The anti-inflammatory activity of 14 2-hydroxy-4-oxo-4-R2-butenoates of heterylammonium has been studied. Five butanoate have an effect lower than comparison drugs, eight compounds are comparable to the effect of reference drugs, one compound is superior to nimesulide. The studied compounds can be assigned to class 4,5 of the hazard classification of chemical products. Medicinal candidates have been selected for further pharmacological, toxicological and technological study.

Действие 1-метил-4-(4-фторфенил)- 1,2,3,6-тетрагидропиридина на биохимические показатели сыворотки крови и обмен моноаминов в головном мозге мышей

Changes in biochemical parameters of blood serum and monoamine metabolism in the brain were studied on male white outbred mice subjected to intraperitoneal injections of 1-methyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (MPTP-F). The levels of norepinephrine, dopamine, serotonin and their metabolites — dioxyphenylacetic, homovanilinic and 5-hydroxyindolacetic acids — were neasured by HPLC in the cerebral cortex, hippocampus, olfactory tubercle and striatum of the right and left sides of the brain. The treatement with MPTP-F did not lead to significant changes in the biochemical parameters of blood serum. An increase in the norepinephrine concentration a decrease in the dopamine level in the right striatum were found in animals treated with MPTP-F. No changes were detected in other studied brain areas. It has been suggested that the effect of the neurotoxin MPTP-F is determined by several factors, i. e. the lipophilic properties of the molecule, the quantitative distribution of dopamine neurons between right and left sides of the brain, differences in the linear velocity of blood flow through the right and left carotid arteries and the state of the blood-brain barrier. The results obtained may indicate the prospects of using MPTP-F for modeling the early stage of Parkinson’s disease.

Biological Activity study of the <i>Melampyrum sylvaticum</i> Extract

Introduction. Among wild plants that have an effect on the nervous system, species of the genus Melampyrum L. are distinguished, in particular, Melampyrum sylvaticum L. Extracts from the aerial part of the plant have long been used in folk medicine as sedatives and anticonvulsants. Currently, a number of studies are being carried out to confirm the possibility of using wildflower and drugs based on it in scientific medicine, as well as to obtain a drug with low toxicity, complex sedative and anticonvulsant activity, which will expand the arsenal of drugs used to treat diseases of the nervous system.Aim. To investigate the in vivo acute toxicity, anticonvulsant and sedative activity of a dry alcohol extract from the aerial part of Melampyrum sylvaticum.Materials and methods. The extract was obtained by extracting substances from the aerial part of Melampyrum sylvaticum with 50 % ethanol, by the method of repercolation with an equal loading of raw materials, followed by evaporation to a dry residue. The study of pharmacological properties was carried out on nonlinear white mice of both sexes weighing 17–25 g. Acute toxicity of the extract was determined by oral administration in doses up to 5000 mg/kg. Anticonvulsant activity was evaluated in the corazole convulsion test, sedative activity was evaluated in the open field test.Results and discussion. When determining the acute toxicity of a dry alcoholic extract from the aerial part of Melampyrum sylvaticum, there was no lethality in the experimental group of animals. LD50 could not be determined. In the corazol convulsion test, it was shown that oral administration of the extract at a dose of 100 mg/kg does not affect the latent period of convulsions, but significantly increases the life expectancy of animals. At a dose of 200 mg/kg, the latent period of seizures and life expectancy significantly increased, and the survival rate of animals was 20 %. When studying sedative activity of the extract from Melampyrum sylvaticum in the open field test, a decrease in vertical activity, a decrease in the number of vertical stands, a decrease in horizontal activity along the periphery and the number of animals entering the center of the area were noted, which indicates a suppression of orienting-exploratory behavior. In the experiment, there was a decrease in the intensity of grooming as an indicator of anxiety for this group of animals. A course of administration of the extract for thirty days led to a decrease in the vertical activity of mice and inhibition of orienting-exploratory behavior.Conclusion. It was found that a dry alcoholic extract from the aerial part of Melampyrum sylvaticum exhibits biological activity in animal experiments, compensating for the effect of corazol, and has a pronounced anticonvulsant and sedative effect. The LD50 of the extract when administered orally was more than 5000 mg/kg.

The Effect of New Water-soluble 2-aminoheteryl-3-ium 4-(het)aryl-2-hydroxy-4-oxobut-2-enoates on the Hemostasis System <i>In vitro</i>

Introduction. The hemostasis system is a set of functional, morphological and biochemical mechanisms of a living organism that ensure the preservation of the liquid state of the blood, the prevention and stopping of bleeding, as well as the integrity of blood vessels. Anticoagulants and hemostatic agents can significantly change the mechanism of hemostasis. Interest in the synthesis and search for compounds that affect the blood coagulation system remains high. Substances exhibiting anticoagulant and hemostatic effects have been found. The search for compounds among the products of organic synthesis that affect the hemostasis system seems relevant.Aim. To study the effect of new water-soluble 2-amino heteryl-3-ium 4-(get)aryl-2-hydroxy-4-oxobut-2-enoates on the hemostasis system using an in vitro model.Materials and methods. Direct interaction 4-(het)aryl-2-hydroxy-4-oxobut-2-enoic acids with heterocyclic amines have been obtained new water soluble 2-aminoheteryl-3-ium 4-(het)aryl-2-hydroxy-4-oxobut-2-enoates. The study of the effect of substances on the hemostasis system was carried out using the coagulometer "APK 4-02-P". Ethamsylate and sodium heparin were used as comparison drugs for hemostatic and anticoagulant activity, respectively. Acute toxicity of the compounds was determined by intravenous administration of aqueous solutions of the compounds to non-linear white mice of both sexes with the definition of LD50.Results and discussion. 10 New 2-aminoheteryl-3-ium 4-(het)aryl-2-hydroxy-4-oxobut-2-enoates have been synthesized. In vitro screening of the effect of compounds on the hemostasis system found that 3 substances have a pronounced anticoagulant effect, and 4 compounds showed hemostatic activity. Some patterns of the "structure-pharmacological action" relationship have been found. The studied butenoates can be classified as moderately toxic compounds according to the classification of chemical toxicity.Conclusion. Pharmacological screening in vitro of the effect of compounds on the hemostasis system was carried out. It was found that all the studied compounds have an effect on the blood coagulation system of varying degrees of severity. The combination of a pronounced pharmacological effect, low acute toxicity and water solubility of butenoates may become a prerequisite for further search and possible development of new domestic medicines that have an effect on the hemostasis system.

Synthesis and antinociceptive activity of 2,2’-(1,4-phenylene)bis[3-aryl-2-azaspiro[3.5]nonan-1-ones

Over the years, azetidin-2-ones, or β-lactams, have received a lot of attention from scientists as potential drug candidates due to their diverse biological activity. Spiro-β-lactams also exhibit biological activity; therefore, it is of interest to synthesize and study the properties of new compounds belonging to this class. The study aims to examine the antinociceptive activity of several synthesized bis(spirolactams), specifically 2,2’-(1,4-phenylene)bis[3-aryl-2azaspiro[3.5]nonan-1-ones]. These bis(spiroazetidine-2-ones) were obtained in the interaction of a twofold excess of the Reformatsky reagent, derived from methyl 1-bromocyclohexane carboxylate and zinc, with N,N-(1,4-phenyle- ne)bis(1-arylmethanimines) by means of boiling them in a 10:1 mixture of toluene and hexamethylphosphorictriamide for four hours. Bis(spiro-β-lactams) on the basis of diimines derived from p-phenylenediamine, 2-methoxybenzaldehyde, p-tolualdehyde, and 3-bromobenzoic aldehyde were synthesized for the first time. The composition and structure of the previously undescribed products were established using IR, [1]H, and 13C NMR spectroscopy and elemental analysis. The antinociceptive activity of the obtained compounds was studied on outbred white mice of both sexes via the hot plate test with an intraperitoneal injection. The effect was estimated two hours after administration. Several synthesized compounds were found to exhibit antinociceptive activity at or above the level of the comparator product – metamizole sodium. Nerve endings can be considered the target of the antinociceptive activity of examined substances since under the effect of these substances, no signs of central action are observed in the behavior of animals. Thus, the conducted studies showed the promise of further search for biologically active substances among the compounds of this series.

Assessing neurotropic effects of new antiepileptic nitrogen-containing drugs

Objective: to evaluate an effectiveness of new nitrogen-containing compounds for alleviating epileptiform conditions in animal experimental study, and conduct molecular modeling of a new neurotropic drug.Material and methods. The anticonvulsant and psychotropic effects of six new heterocyclic compounds synthesized at the Institute of Fine Organic Chemistry were analyzed: № 1 (tetrahydrobenzothienopyrimidine), № 2 (pyridopyrimidine), № 3 (pyranotriazolopyridine), № 4 (thioalkylpyranotriazolopyridine), № 5 (pyrazolyltetrahydrothienoisoquinoline), and № 6 (thioxopyranopyridine). Experiments were carried out with 300 white outbred male mice weighing 18–24 g and 48 male rats weighing 120–150 g. The anticonvulsant spectrum of action was assessed in mice using the following tests: maximum electric shock, corazole-induced seizure. The psychotropic compound-related properties were analyzed using the following tests: elevated plus maze, open field, conflict situation. The neurotoxic compound-related effects were evaluated by incoordination of movements in rotating rod test. Comparison was performed with pufemide (3-(p-isopropoxyphenyl)succinimide), ethosuximide and diazepam.Results. The new nitrogen-containing drugs were revealed to exhibit high anticonvulsant activity, especially observed in corazoleinduced seizure test. All select compounds have anticonvulsant, anxiolytic, psychosedative or behavior-activating effects. Compound № 1 (N3212) is the most effective (median effective dose is 16 mg/kg) in antagonism to corazole action and is significantly superior to ethosuximide and pufemide exceeding by 10- and 5-fold, respectively. The compound shows least toxic (median lethal dose is 2300 mg/kg) and low neurotoxic (median toxic dose is 660 mg/kg) effects. Therapeutic and protective indices for Compound No. 1 exceeds that of ethosuximide by 17- and 13-fold, and of pufemide by 6- and 8-fold, respectively.Conclusion. The select compounds are superior to the approved drugs used in medical practice, pufemide and ethosuximide. A Compound N3212 selected among them may find application as an anticonvulsant drug with psychotropic effects.

Dermapen Treatments for Healing Pockmarked Skin in Male Wistar Rats (Rattus norvegicus): A Study Comparing Platelet-Rich Plasma with Salmon DNA Serum

Skin issues like deep acne scars (pockmarks) are routinely addressed. Dermaroller and Dermapen face skin care help cure this issue. Researchers believe plasma from platelets (PRP) and salmon DNA serum dermapens work similarly on pockmarked skin. White Wistar mice were tested to confirm this suspicion. This is a lab study or an experiment. The study employed a post-test only with a control group design on 16 white Wistar rats (Rattus norvegicus) divided into two groups of eight rats each: Group I received platelet plasma dermapen (PRP) and Group II received salmon DNA serum dermapen. The collected data was tested for normalcy using SPSS. The data normality test showed a significance value of 0.20 > 0.05, indicating normal distribution. The homogeneity test is 0.224. The significant probability value is greater than 0.05, indicating that the PRP dermapen group and the salmon serum DNA dermapen group have similar variances. The t-test rejects H0 or shows a significant difference in wound healing between groups if the significance value is 0.00 or less than 0.05. The study found that PRP and salmon DNA serum promote wound healing. Healing was faster in the PRP than in the salmon DNA serum group. This is possible because PRP includes bioactive molecules that act as tissue growth factors to enhance proliferation. PRP contains various growth factors that aid wound healing.

Bleeding time and clotting time post-extraction Rattus norvegicus tooth treated with ethanol extract gel from Terminalia cattapa L. leaves

Link of Video Abstract: https://youtu.be/iJSDiYl-BmA Introduction: Post-extraction bleeding is a complication that is often encountered in dental practice. A decrease in the number of platelets will increase the risk of bleeding. If left untreated, complications can range from hematoma to severe blood loss. The use of medicinal plants is common in traditional medicine throughout the world. Flavonoids and tannins are the main compounds that play a role in the blood clotting process. The ethanol extract of Terminalia catappa L. leaves contains: saponins, alkaloids, tannins, flavonoids, triterpenoids, and phenols. This research aims to determine bleeding time and clotting time after tooth extraction. White mice were given ethanol extract gel from Terminalia cattapa L. leaves. Method: Study design using randomized with post-test only control group design, in vivo. A population of 35 male white rats (Rattus norvegicus) of the Wistar strain, were grouped randomly into 7 groups. The extraction of white rat teeth using artery clamps, measurement of bleeding time and clotting time using three stopwatches, and the results were averaged. Result: The results of the research showed that the ethanol extract gel of Terminalia cattapa L. leaves had a shorter bleeding time and clotting time than pure gel, after tooth extraction from white rats. Conclusion: Terminalia catappa L. leaf ethanol extract gels have the ability to shorten bleeding time and clotting time and the best gel concentration is 50%.

Molecular biological marker BCL-2: testis analysis in prenatal injection of estrogen to white laboratory mice

Immunohistochemical study is one of the modern methods of disease diagnostics used in practical veterinary practice, as well as in scientific developments in differential diagnostics of animal diseases of tumour and non-tumour nature. Prenatal influence of estrogens results in reproductive system disorders in an adult organism which is accompanied by parallel growth of steroid dependent cancers of the offspring: testicles and ovaries. The aim of the study was to perform immunohistochemical analysis of Bcl-2 marker during prenatal exposure to different doses of the synthetic estrogen analogue Sinestrol in the testes of the offspring of white non-pedigreed laboratory mice. After fertilization, the pregnant females were divided into 3 groups, one intact and two experimental groups. The intact group was unaffected (n = 10). The first experimental group, C-25 (n = 13), was injected with the estrogen drug Sinestrol in the form of a 2 % oil solution at a dose of 25 g/kg. The second experimental group (n = 13) was given the estrogen preparation Sinestrol in the form of 2 % oil solution in a dose of 40 mkg/kg. When the offspring reached sexual maturity, they were removed from the experiment. Immunohistochemical analysis was carried out on sections from paraffin blocks of testes of progeny intended for standard morphological study, the marker of apoptosis inhibitor Bcl-2 was determined on indices of cellular elements of male glands of progeny: spermatogonia, spermatocytes, sperm-tides, spermatozoa and Leydig cells. Expression of Bcl-2 marker upon exposure to the synthetic drug Sinestrol at doses of 25 and 40 g/kg showed that the number of positively stained cells in spermatogonia increased by 8.6 and 9.4 % respectively compared to the intact group. When the intact group was compared with experimental groups C-25 and C-40, the expression of Bcl-2 marker in spermatocyte cells and spermatozoa showed no difference, a slight increase in positively stained cells in spermatids was observed. Bcl-2 marker expression rate in experimental groups C 25 and C-40 decreased in Leydig cells by 56.0 (P 0.05) and 60.0 % (P 0.05), respectively. Administration of the synthetic estrogen analogue Sinestrol during fetal gland initiation resulted in impaired morphology in the testes in adulthood. The expression index of Bcl-2 marker in experimental groups C-25 and C-40 decreased in Leydig cells, resulting in apoptotic cell death, which is responsible for production of male sex hormone testosterone. The results can be used to select optimal doses of the synthetic estrogen analogue Sinestrol in the prenatal period.

The Influence of Flavonoid Compositions on Nrf2 Transcription Factor Expression in Case of Infections Triggered by Influenza A Virus and Transmissible Gastroenteritis Coronavirus

Background. Viral infections trigger transcription factors, including Nrf2, which regulate the expression of genes related to cytokines, chemokines, and more. Nuclear factor erythroid 2-related factor 2 (Nrf2) participates in complex regulatory networks controlling the expression of cytoprotective genes and immune responses. Recently, new roles have been attributed to Nrf2, including the regulation of antiviral responses. Objective. The aim of the study was to analyze Nrf2 activation in influenza virus infection in vivo and in transmissible gastroenteritis coronavirus (TGEV) infection in vitro, as well as the effects of the flavonoid compositions Proteflazidum® and Protoil on the Nrf2 expression in these two experimental models of viral infection. Methods. Outbred white mice were infected with influenza A virus (A/FM/1/47/H1N1 strain). Jurkat cells were infected with TGEV, previously adapted to these cells. Flavonoid compositions Proteflazidum® and Protoil (Ecopharm, Ukraine), containing the mixture of tricin, luteolin, apigenin, quercetin, and rhamnosin, were used in corresponding dilutions. Real-Time PCR was employed to analyze Nrf2 RNA expression in the lungs of mice and in both uninfected and virus-infected cells. Additionally, ELISA was used to assess the expression of Nrf2 peptide. Results. The Nrf2 expression in the lungs of influenza virus-infected mice showed a tendency to increase within a 100-fold range. In virus-infected mice treated with Proteflazidum® or Protoil, the level of Nrf2 expression in the lungs decreased about 10-fold compared to infected untreated mice. TGEV infection resulted in 100-fold increase in Nrf2 expression in Jurkat cells. Both Proteflazidum® and Protoil decreased Nrf2 expression in TGEV-infected cells, while their effects on Nrf2 expression in the intact cells on Day 1 were not detected. Conclusions. Flavonoid compositions have only a slight effect on Nrf2 expression in intact cells. However, in case of virus infection, both in vivo and in vitro, they counteract the extensive up-regulation of Nrf2 expression due to viral infection.

The Effect of Kefir (Cow’s Milk) Administration to Prevent Reduction of SOD (Superoxide Dismutase) Activity in Pregnant White Mice (Rattus norvegicus) Placenta with Cigarette Smoke Exposure

The Effect of Kefir (Cow’s Milk) Administration to Prevent Reduction of SOD (Superoxide Dismutase) Activity in Pregnant White Mice (Rattus norvegicus) Placenta with Cigarette Smoke Exposure

Effectiveness of red betel leaf extract cream for healing burn wounds

Burns are a frequent type of wound that can cause complications, infection and bleeding. The use of plants and natural materials as wound-healing remedies has been known for a considerable period, although more scientific proof is required. The objective of this investigation is to examine the efficacy of red betel leaf extract ointment in curing burns on the backs of white wistar rats. The study used a pre-test post-test design with a control group. Twenty white rat samples were employed. The samples were split into four groups, consisting of five rats each. Betel leaf extract was prepared through maceration, whilst betel leaf extract cream was made using the oil-in-water emulsion method (M/A). A histopathology test was carried out to observe growth of fibroblast cells. Rat skin biopsy was taken from a 2 x 2 cm area, and data normality was tested with the Shapiro-Wilk test (p > 0.05). The One-way Anova test (p < 0.05) was used to assess the differences between the groups. To determine the most effective treatment group, a post hoc test using LSD technique was performed. The findings showed that the average percentage of burn wound healing in the control group (P0) compared to groups P1, P2, and P3 was very different. The analysis reveals that the application of 15% betel leaf extract cream proves to be superior in treating burns in white mice in contrast to 7.5% and 10% betel leaf extract cream. At a 15% concentration, secondary metabolite compounds found in betel leaf extract are already effective in treating wounds. However, at lower concentrations they only inhibit microorganisms, making them less effective in promoting wound healing.

Study of acute toxicity parameters of diclofenac sodium by different methods of administration

Annotation. The purpose of the work was to determine and investigate the parameters of the toxic effect of the substance diclofenac sodium in different ways of entering the body of warm-blooded animals. To achieve this goal, diclofenac sodium was administered to animals once and acute toxic effects were studied in white mice, non-linear white rats, and short-haired guinea pig under the conditions of intragastric, transdermal, and intranasal administration. The criteria for the toxicity of the studied compound (sodium diclofenac) were DL50 and CL50, using the probit analysis method. In addition, a number of toxicity indicators were calculated, in particular, allergenicity, local irritant effect were determined, and the effect on the mucous membrane of the eye. According to the obtained results, the DL50 indicator of diclofenac sodium in mice was 550 mg/kg (intragastric administration); in female rats – 54.83 mg/kg (intragastric administration). The toxicological parameter of diclofenac sodium was obtained – DL50 of transdermal administration for female rats, which is 104.4 mg/kg. It was determined that the CL50 of diclofenac sodium for mice is 71.61 mg/m3, the CL50 for male rats is 243.11 mg/m3. Diclofenac sodium has been found to be non-lethal to ants after a single dermal injection, but can irritate their skin in high concentrations. However, this substance, penetrating through the skin, causes deterioration of health and death of rats. When determining the allergenicity and local irritant effect in animals, it is shown that diclofenac sodium does not have a pronounced irritating effect on the mucous membrane of the eyes and does not exhibit allergenic properties. So, the established indicators of acute toxicity of diclofenac sodium testify to the expediency and perspective of further determination of cumulative characteristics during multiple intragastric, intranasal administrations and skin applications in order to establish and justify the maximum permissible concentration of diclofenac sodium in the atmospheric air of populated areas.

Research on the embryotoxic effect and carcinogenicity of the drug “BTF plus” – a means for normalizing metabolic processes in animals and poul-try

Laboratory studies were conducted to determine the embryotoxic effect and carcinogenicity of the veterinary drug “BTF plus” on white rats and white mice. The drug “BTF plus” is a complex vitamin-mineral drug based on butophosphane, L-carnitine, and cyanocobalamin, which is used to normalize and correct metabolic processes in animals and poultry. The drug is used for various types of animals and poultry as a stimulating, tonic and general strengthening agent for obstetric pathologies (complicated childbirth, postpartum complications, paresis, eclampsia, sexual cycle disorders); metabolic disorders caused by irrational feeding, malnutrition, asthenic syndrome, etc.; anemia with helminthiasis; secondary anemias, as an additional means in the treatment of magnesium and calcium deficiency; to increase muscle activity, with significant loads, overstrain and exhaustion in animals; to increase the body's resistance to various pathogens; to stimulate growth, development and live weight gain in young animals and poultry; as an additional means in the treatment of diseases caused by various factors (infectious and non-infectious origin). The drug “BTF plus”, under the conditions of subcutaneous administration to pregnant female rats in doses (based on the absolute weight of the drug) of 200.0 and 2000.0 mg/kg of body weight, does not cause death and pathological changes in embryos do not have an embryotoxic and teratogenic effect since indicators of total, preimplantation, and postimplantation embryonic lethality in rats of the experimental groups had no significant differences compared to indicators in control and also did not show changes in the weight of the placenta, fetuses, and their cranio-caudal size. The drug “BTF plus”, under conditions of 5-day subcutaneous administration to white mice in doses (based on the absolute weight of the drug) of 200.0 and 2000.0 mg/kg of body weight, does not show a carcinogenic effect (during microscopic studies, the proportion of polychromatophilic erythrocytes was not probable deviations between themselves and was 0.117-0.133%, which is within the normal range of up to 0.2 %). Further studies will be the next stage of pre-registration tests aimed at studying the ecotoxicity of “BTF plus”, which is a mandatory material of the “Safety and residue studies” section of the dossier for this drug.

Acute toxicity of zinc carbonate nanocrystals on white mice model

Zinc-based nanoparticles (NPs) are successfully used to meet the mineral needs of animals and poultry, capable of increasing the growth rate and the efficiency of their use of feed. Nanoparticles of zinc oxide are widely used, which are superior to conventional sources of zinc in terms of pharmacological activity and bioavailability, have a positive effect on productivity and antioxidant protection, and increase reproductive potential. However, a detailed investigation of their toxicological parameters showed the risks of their introduction into the body, as a result of which a large number of zinc oxide NPs were synthesized by the methods of “green chemistry”, the main drawback of which is a complex methodology and a high level of costs. We investigated the acute toxicity of a colloidal solution of zinc carbonate nanocrystals in a model of white mice. The experiment was conducted on 42 female non-linear white mice, 3–4 months old, with a live weight of 21–23 g, kept under optimal vivarium conditions. According to the principle of analogues, 6 experimental groups were formed: mice were injected with a colloidal solution of zinc carbonate nanoparticles in doses (by absolute weight of the drug) of 15,000.0; 20000.0; 25000.0; 30000; 35000.0 and 40000.0 mg/kg of body weight based on the absolute weight of the drug, which according to the active substance (zinc carbonate nanoparticles) was (37.5; 50.0; 62.5; 75.0; 87.5 and 100, 0 mg/kg of body weight), orally using an esophageal-gastric tube. Mice of the control group were injected with distilled water in a volume of 0.2 cm3 according to the same protocol. The clinical condition of the experimental animals was observed for 14 days, noting the appearance and development of clinical signs of poisoning, the time of death or recovery to the physiological norm. After the death (diagnostic slaughter) of the animals, a pathological autopsy was performed. Clinical observations showed that a single intragastric administration of the drug to mice of experimental groups 1-6 did not cause acute poisoning. The deaths of mice in all experimental groups were not observed during the 14-day observation period, as a result of which the LD50 indicator could not be calculated. At the same time, the maximum possible injected dose of the colloidal solution of zinc carbonate nanoparticles (by absolute weight) was 40,000.0 mg/kg of body weight (100.0 mg/kg by active substance), which allows the drug to be assigned to the VI class of toxicity – substances are relatively harmless (LD50 > 15000.0 mg/kg of body weight), and according to the degree of danger up to IV class – low-hazardous substances (LD50 > 5000.0 mg/kg of body weight).

Evaluation of the anxiolytic activity of dry extract of Patrinia scabiosifolia under acoustic stress.

Patrinia scabiosifolia has been used in traditional medicine in East Asia, Africa, and South America for a variety of diseases for more than 2000 years. The purpose of the article is to evaluate the anxiolytic properties of dry extract of P. scabiosifolia. In vivo experiments were performed on outbred white male mice. The psychotropic effect of P. scabiosifolia dry extract was assessed using behavioral test systems aimed at identifying changes in the psycho-emotional state of animals under the influence of acoustic stress. In addition, the preparation toxicity was also assessed. HPLC-MS analysis was carried out to confirm the presence of active components in local raw materials. The article describes the possibility of using dry extract of P. scabiosifolia as an anxiolytic and sedative for psycho-emotional stress in experimental animals. Based on comprehensive research results, the effectiveness and safety of the studied herbal preparation have been proven. In this study, a dry extract of P. scabiosifolia has been proposed as a novel means of combating neuropsychiatric disorders. P. scabiosifolia showed efficacy comparable to the reference drug (Mebicar), reducing sleep time and increasing sleep duration. The results obtained can subsequently serve as the basis for clinical trials.