Organs Of Experimental Animals Research Articles

Mitochondrial donation as a mechanism of participation by mesenchymal stromal cells in regenerative processes

Mesenchymal stromal cells (MSCs) are universal regulators of regenerative processes due to their ability to secrete regulatory molecules or replace dead cells through differentiation in the appropriate direction. Recently, another mechanism for the beneficial effects of MSCs on damaged tissue has been discovered, such as the transfer of mitochondria into its cells in response to stress signals. MSCs can transfer mitochondria through tunneling nanotubes that form a communication bridge between cells, through gap junctions, by release as part of extracellular vesicles or in free form, and as a result of complete or partial fusion with recipient cells. In damaged cells that received mitochondria from MSCs, impaired energy metabolism is restored and oxidative stress is reduced, which is accompanied by increased survival, and in some cases also increased proliferation or a change in differentiation status. The restoration of energy after the transfer of mitochondria from MSCs has a beneficial effect on the functional activity of recipient cells and suppresses inflammatory reactions. A significant contribution of the MSC mitochondrial donation to the therapeutic efficacy of MSCs has been repeatedly demonstrated in models of damage to various organs in experimental animals. This stimulates the search for methods to enhance the process of mitochondrial donation. However, it should be taken into account that MSCs are able to transfer mitochondria to malignant cells as well, thereby stimulating tumor growth and increasing its resistance to chemotherapy. These data make it necessary to evaluate the prospects for the use of MSCs in cell therapy with caution. On the other hand, they can serve as a basis for the search for new therapeutic targets in the treatment of oncological diseases.

Effect of chronic intake of cadmium chloride on the transcriptional activity of metallothionein and zinc transporter genes

Introduction. Cadmium chloride is an inorganic compound containing cadmium, a heavy metal that is one of the active environmental pollutants today. Damage to organs in experimental animals due to cadmium poisoning is similar to that in humans. In this work, the activity of metallothionein and zinc transporters genes was studied in a chronic model of cadmium-induced poisoning in experimental animals.
 Materials and methods. The experiment was carried out using seventy two individuals of white inbred rats of both sexes, the average weight of which was 215 g. Animals from four groups were injected with a solution of cadmium chloride in four different doses, respectively, individuals of the fifth group, the control group, received an equimolar volume of pure water. The objects of the study were the kidneys and livers of rats, removed after the animals were withdrawn from the experiment. Next, the activity of the Mt1A, Mt2A, Mt3A, Zip1 and Znt1 genes was analyzed in organ samples using real-time PCR.
 Results. Significant increases in the expression multiplicity of Mt1A, Mt2A and Mt3A metallothionein genes in the kidneys at different doses of the toxicant were revealed. In liver samples, a decrease in the expression of the Mt2A gene was found in the experimental group exposed to cadmium chloride at a dose 
 of 0.1 mg/kg (p<0.05). For the Znt1 gene in rat liver tissue, there was a statistically significant decrease in expression at a dose of 0.001 mg/kg (p<0.05) 
 and, conversely, an increase at doses of 0.1 and 1 mg/kg (p<0.05) compared to the control group. Analysis of the level of transcripts of the Zip1 gene in the kidneys and liver after 6 months of inoculation with the toxicant in the presented doses did not reveal statistically significant differences between the groups.
 Limitations. Laboratory animals of the only biological species were used for the experiment. Four doses of the cadmium salt alone were evaluated.
 Conclusion. The results obtained allow concluding that the level of expression of the Mt1A, Mt2A and Mt3A genes in the kidneys can play the role of a diagnostic marker in chronic poisoning with the toxicant under study.

Grzyby pleśniowe w środowisku człowieka – lekceważone niebezpieczeństwo

IntroductionAccording to Dz. U. nr 75 of 15 June 2002, building law does not allow visible signs of mold fungi in rooms used by people and imposes immediate renovation because of exposure to spores. Which being absorbed via airway and skin may be main sources of three forms: infection, allergy and toxicity. Mycotoxins get to the organism via digestive tract or airway with dust particles or food.Caused illnessesDry eye syndrome, eye socket necrosis, acute, persistent poisoning, impaired immunity, sinusitis, pharyngitis, bronchitis, pneumonia, asthma, air and skin allergy, headache, muscle aches, artralgia. Constant irritability, fatigue, insomnia, reduce concentration, memory disorder, even depression. In the digestive tract disturb metabolism, in extreme cases causing cirrhosis, even cancer; disorder pancreas, ovaries, prostate, and lead to sterility, kidney dysfunctions. Growth of fungi is connected with insufficient heating and ventilation. It is derivative socio-economic factors, hygiene level and health care.PurposeIs presentation of the resulting threat from fungal spores and toxins exposure which are inside our houses, schools, hospitals, even our food based on available medical literatureConclusionsMold Fungal toxins have an effect teratogenic, mutagenic and genotoxic inducing damaging many organs in experimental animals. Illnesses and deterioration of health are not connected with spores and toxins exposures. It may lead to wrong diagnosis and not eliminate fungi from the environment, what cause exacerbating symptoms. Fungal infection may be similar to other illneses as: tuberculosis, molluscum contagiosum, cryptococcosis, histoplasmosis what can delay proper diagnosis and significantlyreduce chances of survival. Species: <i>Cladosporium, Alternaria, Aspergillus</i> and <i>Penicillium</i> were found in high concentrations ta astmatic patients houses. It was connected with asthma symptoms deterioration in 36% to 48% cases.

Immunological Properties of The Effect of Acute Exposure on The Organism of Experimental Animals

The aim of the study was to determine the effect of acute irradiation on the immune status of experimental animals, taking into account the degree of influence of biocorrection on this process. It was found that in white outbred male rats that received and did not receive acute irradiation, distinctive results were obtained in the relative values of immune system cells. This was observed in the total number of lymphocytes, cells - CD3+-, CD4+- and CD8+. A key indicator of the development of secondary immunodeficiency is a decrease in IRI by 2.01 times in the main group. No changes were found in CD20+ cells, in the main group of laboratory animals the number of CD16+ cells increased by 1.35 times, and in CD95+ cells it decreased by 1.51 times. The deficiency of the immune system in the biocorrection group was relatively shallow, the biological product used had an immunostimulating effect. It has been proven that its use reduced the negative impact of acute irradiation on the quantitative indicators of immune system cells.

Structural rearrangement of organs of white mice vaccinated with Yersinia pestis EV in combination with organoselenium compound 974zh

Introduction. An urgent direction is the search for means that increase the effectiveness of the Y. pestis EV NIIEG vaccine and reduce the side pathological manifestations caused by it. Organoselenium compounds have immunotropic properties and increase the antioxidant potential of the body, as well as have an antidystrophic effect and an antiallergic effect. Materials of the study of the immunomodulating effect of the experimental selenium-containing compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the macroorganism of laboratory animals are presented.The aim. To evaluate the effect of the organoselenium compound 974zh on the structural rearrangement of the organs of experimental animals in the dynamics of the vaccine process caused by Y. pestis EV.Methods. The study was carried out on 70 certified outbred white mice. Histological material (thymus, lymph nodes, spleen, adrenal glands, liver) was embedded in paraffin, semi-thin sections were stained with hematoxylin and eosin, thionin, and by the Brachet method. The severity of pathological changes in the liver and adrenal glands, proliferation of plasma cells and structural changes in immunocompetent organs (thymus, lymph nodes and spleen) were assessed. Microphotography and quantitative analysis were performed using MoticImagesPlus 2.0. Statistical processing was carried out using the computer program Statistica.Results. It has been established that the combined administration of 974zh and Y. pestis EV leads to morphological and functional restructuring of immunocompetent organs, enhances the proliferation of plasma cells in the spleen and lymph nodes, and eliminates negative changes in the liver and adrenal glands. Conclusion. Thus, the 974zh preparation enhances the immunogenic effect of the Y. pestis EV vaccine strain, increasing the T- and B-dependent zones of the spleen and lymph nodes, increasing the proliferation of plasma cells, and also significantly reduces pathological changes in the liver and adrenal glands.

The Effects of Exposure Methods on the Toxicity of Zinc Oxide Nanoparticles

In recent years, with the widespread use of zinc oxide (ZnO) nanoparticles (NPs), more and more attentions are being given to its biological toxicity, the toxicity of ZnO NPs under different exposure methods is necessary to investigate. In this study, we prepared two ZnO dispersions with different particle sizes, namely small-size ZnO (S-ZnO) and Bigsize ZnO (B-ZnO), using polycarboxylic acid as dispersant. Mice were poisoned by intravenous injection and inhalation, respectively. The respiration coefficient, superoxide dismutase (SOD), Zn content in the organs of the mice were detected. It was discovered that ZnO NPs with smaller particle diameter can cause more serious toxicity in vivo after intravenous exposure and respiratory exposure. In addition, the mice showed symptoms of dyspnea after respiratory exposure and a massive number of fibroblasts were found in the alveolar structure of the lungs. In the intravenous injection group, the content of Zn in the liver and spleen of mice increased significantly, resulting in organ edema, and the organ coefficient of mice increased. Finally, the increase of GSH/GSSG indicated that cells were regulated under the antioxidant mechanism, which accelerated the removal of H2O2 from cells. In addition, the increase of GSH+GSSG content also indicated that ZnO NPs stimulated the creation of reactive oxygen species (ROS) in organs of experimental animals.

Эффективность минерального адаптогена в условиях экспериментальной иммуносупрессии

Abstract. Modern conditions of animal husbandry and poultry farming dictate a continuous search for effective means that increase the natural resistance of the organism of farm animals and poultry. The purpose of the study. In this regard, an experimental study was conducted on laboratory animals using a mineral adaptogen of domestic production in order to determine its effectiveness in conditions of artificially induced immunosuppression. The objectives of the study were to determine the immunobiochemical status, subcellular and intra-organ changes in the organs of the immune system at all levels. Research methods. Experimental studies were carried out using generally accepted zootechnical, pathomorphological, histological, immunobiochemical and statistical research methods. Results. Immunobiochemical changes in the body of experimental animals are described. Microscopic changes at the level of tissues and cells in the organs of the immune system at all levels are described. Changes in the organs of the immune system during immunosuppression and against the background of feeding mineral adaptogen are described. Morphological examination of the immune system organs in experimental animals revealed prolonged immunosuppressive changes for 14 days. At the same time, after induced immunosuppression, significant structural changes remain in the central and peripheral organs of the immune system in the form of lymphoid tissue atrophy (in the thymus, both in the organ of central immunogenesis and in the organs of the peripheral immune system – the spleen and lymph nodes and intra-organ lymph formations). During histological studies, the structure of cells and tissues, when using a mineral adaptogen, was more morphologically mature and was in a functionally active state, and dystrophic and necrotic processes were observed in the control group. The conducted studies convincingly prove the effect of mineral adaptogen on increasing natural resistance and its immunoprotective properties. Scientific novelty. For the first time in experimental conditions, a simultaneous assessment of the immunobiochemical parameters of the blood of laboratory animals and a microscopic examination of the organs of the immune system at all levels with morphometric analysis of the data obtained were given. As a result of the conducted studies, the immuno- and organoprotective effect of feeding the mineral adaptogen was proved and the immunomodulatory effect was morphometrically confirmed.

Accumulation of cadmium in organs of experimental animals and its effect on the content of essential elements in the chronic intoxication

Introduction. This article presents the results of studying the effects of cadmium chloride and its accumulation in experimental animals’ liver, kidneys, and blood. The impact of cadmium consumption on basic bioelements (zinc, copper, calcium) in organs was assessed. Materials and methods. Experimental groups of white outbred rats were exposed daily for three months to a cadmium chloride solution containing 1, 10 and 100 μg of cadmium. Cadmium exposure was assessed at 1, 4, 12, 30, 60 and 90 days. The concentrations of cadmium, calcium, copper and zinc were measured by atomic absorption spectrometry. Results. Whole blood cadmium concentration was not statistically different from the control group. The accumulation of cadmium in the blood was observed only after three months of exposure to a dose of 100 μg. The accumulation of cadmium in the liver occurred after one and two months of intoxication, depending on the dose. In the kidneys, an increase in cadmium occurred in all experimental groups after one month of injection. The metal content depended on the level of exposure, but no difference was observed between the liver and kidney. The concentration of zinc and calcium decreased in the kidneys and liver. Conclusion. Changes in calcium and zinc, accompanied by elevated levels of cadmium in the liver and kidneys, suggest that cadmium may interfere with the biological processes in which these elements are involved.

EVALUATION OF PATHOGENICITY OF NODULE BACTERIA STRAIN RHIZOBIUM LEGUMINOSARUM G 222

Objective. Investigate pathogenic (non-pathogenic) properties of a new strain of nodule bacteria Rhizobium leguminosarum G 222. Methods. Microbiological (obtaining a suspension of R. leI guminosarum G 222, determination of its titre by opacity optical standard and by seeding on a digest medium; microscopy of stained imprint smears of internal organs of experimental animals and seeding of tissue samples on a digest medium), pathoanatomical (to determine possible invasiveness and dissemination of bacteria in the tissues of internal organs of animals — in the model of outbred white mice after administration of a suspension of live bacterial cells (oral doses from 0.5 × 109 to 5 × 109 CFU in 0.5 cm3 of sterile isotonic sodium chloride solution per mouse and intraperitoneal doses from 1 × 109 to 5 × 109 CFU/0.5 cm3) and statistical. Results. Over 15 days of observations after administration of a suspension of live bacterial cells, no death of experimental animals was registered. The strain did not lead to any changes in the general condition of the mice. No changes in their behaviour were reported. Fifteen days after the start of the study, it was found that this strain is non-infective (non-invasive), does not disseminate and does not reproduce in the body of experimental animals. Oral and intraperitoneal doses of a suspension of live bacterial cells did not result in bacterial invasion of animal internal organs. No retrocultures were registered. Gross examination did not find characteristic changes in the internal organs of the experimental animals. The obtained results indicate the avirulence of the strain for the studied warm-blooded animals (intraperitoneal LD50 > 5 billion cells/mouse, oral LD50 > 5 billion cells/mouse). Conclusion: According to the results regarding the lack of virulence and according to regulations, the new strain R. leguminosarum G 222 belongs to the group of avirulent microorganisms that are not able to invade the internal organs of studied warm-blooded laboratory animals and can be considered nonpathogenic and used as a basis for microbial preparations to increase crop yields.

CLINICAL TRIALS OF VETASEPTOL FOR THE TREATMENT OF CALVES WITH SIGNS OF ACUTE INTESTINAL INFECTION

The aim of the present study was to investigate of the therapeutic efficacy of the two- components antimicrobial drug. The drug contains two antimicrobial components that act synergistically. Acute intestinal infection of calves was treated. The drug was given with food. The dose and method of administration were determined by the manufacturer. Before use, the sensitivity of pathogenic microorganisms to the active components of the drug was determined. During the experiment, constant monitoring of the clinical condition and physiological parameters of the organism of experimental animals was performed.
 Evaluation of hematological and biochemical parameters of the body was performed according to recognized methods. Therapeutic efficacy was compared with data obtained using the reference drug. The obtained data were processed statistically. Based on the obtained data, conclusions were made about the effectiveness of treatment and the effect of the drug on the body of young cattle.
 According to the assessment of the clinical condition of the animals and the results of laboratory studies, it was found that the tolerability of the study drug for the treatment of intestinal infections in young animals was good. During the experimental period and two weeks after the use of drugs, no side effects were detected and no changes in the behavior of calves were observed. The therapeutic efficacy of the study drug was 100 %, and the recovery period was 5 days. Comparative analysis of hematological parameters of calves showed a significant decrease in the percentage of rod-shaped neutrophils in the leukogram of sick animals after antibiotic therapy. Normalization of the leukogram indicated the cessation of inflammatory processes and improvement of the physiological condition of animals. Analysis of the influence of drugs on biochemical indices in experimental calves showed no changes during the observation period. Negative impact on liver indicators under administration weren't found. Laboratory studies have not revealed nephrototoxic effects of antimicrobial drugs. Confirmed the safety and therapeutic efficacy of the two antimicrobial components drug.

Changes in the Organs of Experimental Animals in the Dynamics of the Infectious Process Caused by <i>Bacillus Anthracis</i> with Different Plasmid Profiles

Background. The current direction is the study of anatomical and histological changes caused by the causative agent of anthrax with a different plasmid profile. It was found that Bacillus anthracis strains with the same set of plasmids and the same morphological, serological and cultural properties sometimes have different pathogenicity. Aim of the study. Comparative analysis of anatomical and histological changes in the organs of experimental animals in the dynamics of the infectious process caused by the pathogen B. anthracis with different genotypes. Methods. Four strains were used as the study object: B. anthracis I-275 (pCO1 – / pCO2 – ), B. anthracis I-323 (pCO1 – / pCO2 – ), B. anthracis I-217 (pCO1 + /pCO2 – and B. anthracis 34F Stern pCO1 + /pCO2 – ). The study was conducted on 260 certified white mice. Histological material was embedded in paraffin, semi-thin sections were stained with hematoxylin-eosin, thionine, and according to Brachet. The severity of pathological changes, the presence of the pathogen, and the proliferation of plasma cells were evaluated. The changes detected during the autopsy of the animal and the results obtained during the histological examination of the anatomical material were analyzed and generalized. Microphotography and quantitative analysis of plasma cells were performed using the “Motic Images Plus 2.0” application software package. Statistical processing of the obtained data was performed using the computer program “Statistics”, version 6 (Novosibirsk). The results were considered reliable if the probability of error was less than 0.05 (p < 0.05) in relation to the control. Results. Differences in anatomical and histological changes in organs and tissues of white mice infected with B. anthracis with the same set of plasmids were revealed. It was found that in animals infected with non-plasmid strains of B. anthracis, the proliferation of plasma cells is significantly reduced compared to animals infected with singleplasmid strains of the anthrax pathogen. Conclusion. The obtained data suggest that the revealed differences are related to the plasmid profile of the studied strains, but also to the peculiarities of their enzymatic activity, adhesion ability, and other factors. Thus, anthrax strains that have the same morphological, serological and cultural properties sometimes have different virulence. And also, anthrax strains that have lost virulence lose their immunogenicity, as evidenced by the ratio of plasma cells.

Gaining acceptance in next generation PBK modelling approaches for regulatory assessments – An OECD international effort

Physiologically Based Kinetic (PBK) models are valuable tools to help define safe external levels of chemicals based on internal doses at target organs in experimental animals, humans and organisms used in environmental risk assessment. As the toxicity testing paradigm shifts to alternative testing approaches, PBK model development has started to rely (mostly or entirely) on model parameters quantified using in vitro or in silico methods. Recently, the Organisation for Economic Cooperation and Development (OECD) published a guidance document (GD) describing a scientific workflow for characterising and validating PBK models developed using in vitro and in silico data. The GD provides an assessment framework for evaluating these models, with emphasis on the major uncertainties underlying model inputs and outputs. To help end-users submit or evaluate a PBK model for regulatory purposes, the GD also includes a template for documenting the model characteristics, and a checklist for evaluating the quality of a model. This commentary highlights the principles, criteria and tools laid out in the OECD PBK model GD, with the aim of facilitating the dialogue between model developers and risk assessors.

Method For Determining The Content Of Toxic Substances In The Liver After Exposure To Pesticides In Experimental Animals

This scientific work is devoted to the study of the results of the action of pesticides on the organism of experimental animals. At the beginning, a brief review of the literature devoted to this problem is given. The author also describes a method for determining the content of toxic substances in the liver tissues of experimental animals. The corresponding conclusions on the simplicity of the method are made.

Features of the sensitivity of the central nervous system of the organism of experimental animals to the effects of certain psychotropic drugs and their combinations against the background of chronic alcohol intoxication in a chronopharmacological experiment

In a chronopharmacological experiment, the effect of two drugs with psychotropic action in combinations on the behavior of laboratory animals subjected to chronic alcohol intoxication was examined. Against the background of a deprimating agent, a decrease in the threshold of sensitivity to electrical irritation and the duration of an aggressive reaction was revealed; an increase in these indicators was established with a combination of a deprimating drug with an antioxidant. It has been shown that the antioxidant has a desynchronizing effect on the behavioral reactions of laboratory animals for two days, which indicates a pronounced adaptive effect. In the case of using combinations of a deprimating agent with an antioxidant, a decrease in the destruction of the histological structure of the myocardium against the background of chronic alcoholization was established.

Chronopharmacological sensitivity of the central nervous system of the organism of experimental animals to the action of certain psychotropic drugs against the background of chronic alcohol intoxication

The behavior of experimental animals under the influence of two drugs with psychotropic action and their combination against the background of chronic alcohol intoxication in a chronopharmacological experiment was studied. A decrease in the threshold of sensitivity to electrical irritation was revealed against the background of the use of a deprimating agent and an increase in these indicators when this drug was combined with an antioxylant. The pronounced adaptive effect of the antioxidant is evidenced by its desyn chronizing effect on the behavioral reactions of laboratory animals for two days.

Features of the sensitivity of the central nervous system of the organism of experimental animals to the effects of certain psychotropic drugs and their combinations against the background of chronic alcohol intoxication in a chronopharmacological experiment

In a chronopharmacological experiment, the effect of two drugs with psychotropic action in combinations on the behavior of laboratory animals subjected to chronic alcohol intoxication was examined. Against the background of a deprimating agent, a decrease in the threshold of sensitivity to electrical irritation and the duration of an aggressive reaction was revealed; an increase in these indicators was established with a combination of a deprimating drug with an antioxidant. It has been shown that the antioxidant has a desynchronizing effect on the behavioral reactions of laboratory animals for two days, which indicates a pronounced adaptive effect. In the case of using combinations of a deprimating agent with an antioxidant, a decrease in the destruction of the histological structure of the myocardium against the background of chronic alcoholization was established.

Peculiarities of the course of radiation-mechanical injuries during modeling of bone-muscular trauma of the limbs in expirement

Experimental data on the course of the wound process and changes in the internal organs of animals during acute radiation sickness are presented. Morphological changes in the wound and with a fracture of the femur, on the model of combined radiation-mechanical conduction in 30 experimental animals (rats). It was found that wounds after primary surgical treatment often suppurate, and the performed osteosynthesis in fractures of tubular bones turns out to be an untenable delivery of metal structures. An unfavorable course of the wound process is noted in the form of pronounced purulent-necrotic changes in soft tissues, which leads to the appearance of degenerative-dystrophic changes in internal organs in experimental animals. The development of the infectious process in the wound, radiation damage is more severe, while the lethality increases by 2023%. The total area and thickness of the newly formed granulation tissue is 1,52 times less than in non-irradiated animals. As a consequence of the disturbance of reparative processes during the development of the mutual burdening syndrome, the consolidation of the fracture with radiation injury to rats was completed in 28,51,2 days, while in non-irradiated animals it was already by 2023 days. The reason for the death of animals is purulent-septic complications in 21 (73%) irradiated rats. Sepsis due to St. aureus was noted in 14 (66,6%) rats and St. epidermalis in 2 (9,5%) animals. Colibacillary sepsis was recorded in 5 (23,8%) rats. Thus, in the conditions of the use of weapons of mass destruction, radiation-mechanical damage will occupy one of the leading places in the structure of sanitary losses. At the same time, the simultaneous effect of radiation and a mechanical factor on the body forms one of the most dangerous variants of damage, in which a favorable outcome is predicted only in milder forms of acute radiation syndrome and provided that surgical treatment is timely.

Study of biological properties of bovine foamy virus on the model of laboratory animals

Genetic material of the field isolate of bovine foamy virus was inoculated subcutaneously in rabbits (5 experimental and 5 intact animals). The influence of genetic material on the organism of experimental animals was studied at the molecular-genetic, cellular, and biochemical levels. It has been established that the persistence of the causative agent of spumavirus infection according to the results of molecular and genetic research (PCR) is 60 days. Redistribution of cells of leukocyte fraction towards lymphocytosis (80–88%) was recorded. Decrease in the concentration of circulating immune complexes by 22.2% (p ≤ 0.05) and a tendency to decrease in the seromucoid concentration (by 6.5%) were found on 60th day after infection compared with control indicators. At the end of the experiment it was established a statistically significant decrease in the concentration of circulating immune complexes and an increase in seromucoid level by 21.5% and 17.6% respectively, as well as a tendency to decrease in the level of globulins, which was 15.5%. The results of hematological and biochemical analysis indicate the development of immunosuppressive state under the influence of the inoculated material

DETERMINATION OF ACUTE AND SUBACUTE TOXICITY OF THE DRUG BASED ON CHLORTETRACYCLINE HYDROCHLORIDE

The article presents the results of determination of acute and subacute toxicity of the drug "Chloracil", which was made on the basis of chlortetracycline hydrochloride. In result of the conducted researches, it was found out, that a single intragastric administration of the drug according to SOU 85.2-37-736: 2011 belongs to the 4th class of toxicity - low-toxic substances.
 In determining the toxicity of the drug by the long-term use, it was found out, that the use of Chloracil in therapeutic and in 10 times higher than the therapeutic doses did not cause death of white rats. The animals of the experimental groups were active, ate well food , and the general condition of the animals did not differ from the condition of the animals of the control group, but there was a tendency to decrease the weights of liver, spleen, heart, lungs, thymus and kidneys on the background of an increase of body weight by 3.4 and 7.3% (p <0.05), compared to the values of the control group. Therefore, the use of the tested drug in above doses for 14 days does not significantly affect on the functional state of the internal organs of experimental animals.
 The study of the effect of the drug on the hematological parameters of blood by long-term use showed that in therapeutic and in 10-time higher therapeutic doses observed a tendency to decrease the hemoglobin concentration, amount of erythrocytes, leukocytes, hematocrit value, on the background of a slight an increase of platelet. In determining the value of erythrocyte indices, it was noted that the use of the drug "Chloracil" in animals of I and II experiments did not cause significant changes in mean corpuscular hemoglobin (MCH). Mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) were at the level of the control group.
 When studying the effect of the drug on the biochemical parameters of blood serum in animals of I and II experimental groups, there was a tendency to decrease the level of creatinine, activity of AST, ALT and LP activity on the background of a slight an increase of total protein content.
 Analysis of the obtained data shows that the use of the drug "Chloracil" to white rats for 14 days in therapeutic and in 10-time higher therapeutic doses caused a slight decrease in the weight of internal organs, hematological and biochemical parameters of blood, which that in turn did not significantly effect on the general condition of animals.

Toxicokinetics of aluminum in rats

Introduction. Aluminum is one of the most common elements in nature that is potentially toxic to humans. Aluminum compounds are widely used in the aviation and food industries, metallurgy, electrical engineering, and medicine. Aluminum is capable of accumulating in the human body, which creates a risk for the development of severe diseases. Material and methods. Acute intoxication of aluminum hydroxide was simulated on white outbred rats weighing 170-220 g, divided into 8 groups (intact and 7 experimental). By the atomic absorption method, the concentrations of aluminum, calcium, magnesium, and iron in the organs of laboratory animals (kidneys, liver, blood, and brain) were determined 1, 2, 4, 6, 24, 48, and 96 hours after intoxication. Results. The accumulation of aluminum was observed to a greater extent in the liver, kidneys, blood, to a lesser extent in the brain. Aluminum affects the homeostasis of essential elements, for example, in the experiment, a decrease in the content of calcium and magnesium in the organs of laboratory animals is observed. The seed level does not have a strong effect on the level of iron. At the end of the experiment, the concentration of aluminum in the liver, blood, and brain of rats remains higher than in the control group. Conclusion. Aluminum is capable of accumulating in vital organs and affecting the homeostasis of the essential elements of the body. The circulation of aluminum in the biological media of a living organism, like many processes, is undulating, and it can accumulate and diffuse for a long time in various organs of experimental animals.