Today, toxicological and pharmacological studies it is difficult to imagine without the biochemical and hematological analysis.
These figures are extremely important for the evaluation: the effect of the study drug on organs and tissues, the body of the target, generated correctness of Experimental Pathology. On the basis of biochemical and hematological analysis can be judged on the protein, fat, carbohydrate and mineral metabolism in the body. Identified during these laboratory tests can detect abnormal changes in various organs and systems.
Today, assessment of biochemical parameters used for the analysis of not only blood, but also for the analysis of urine, bronchoalveolar lavage (flushing), exudate, bile, tissues.
Evaluation of cellular structure also holds not only for blood but for bone marrow, bronchoalveolar lavage (flushing), exudate, urine, other biological fluids.
All materials used in laboratory methods for determining passed the validation process (and/or verification) in line with modern requirements. Team members conduct regular intralaboratory quality control laboratory tests.
Employees of the group of Biochemistry and Haematology are high-level experts, regularly undergoing further training. In the group there are three candidates of sciences, doctor of clinical laboratory diagnostics, laboratory assistant.
Research carried out on an automatic biochemical analyzer “A-25” company “Biosystem” (Spain). The analyzer allows you to determine in biological fluids full range of biochemical parameters, such as carbohydrate, protein, lipid and mineral metabolism that characterize the work of bodies, organs and body systems as a whole.
To identify additional markers of various pathologies in the laboratory are used by ELISA analysis.
Hematological analysis to determine the blood of various animals (rats, rabbits, hamsters, guinea pigs, ferrets, mini-pigs, etc.), specialized veterinary analyzer: «Abacus Junior Vet», and «Mythic-18-Vet». If necessary, blood smears are performed manually.
Schematic representation of the blood cells Reticulocytes in blood smear of a rabbit
In the peripheral blood lymphocyte rat
Storage stained smears
Urine analysis is performed on a portable analyzer HandUReader urine (“77 Elektronika Kft.», Hungary). With the help of the analyzer is performed semi-quantitative determination of the concentration range (level) of analytes in automatic mode using the test strips dry chemistry method.
If necessary, carry out evaluation of the urine sediment microscopy it is counted in multiple fields of view at high magnification microscope content of formed elements, bacteria, epithelial cells, crystals.
The crystals (salt)
When working with experimental animals after bone marrow extraction from the proximal femur prepare smears using cytological centrifuge and stained them Mine-Grunwald are stained with Giemsa.
Myelogram healhy rats
The impact of various factors (drugs, ionizing radiation, toxic agents, xenobiotics, etc.) provokes not only quantitative changes in myelogram, but also qualitative changes in the structure of cells of various germs hematopoiesis. Quantitative changes can be characterized by an increase in blast cells, the proliferation of the germ and the oppression of the other, the imbalance of cell structure, or cytopenia hypercellular. Qualitative changes may be characterized by multinuclear cells, megaloblastoidnostyu, dissociation in maturation of the nucleus and cytoplasm, karioreksisom, supervision internuclear bridges, and the appearance of cells Joly Case, punktatsiey basophilic erythrocyte hypersegmentation neutrophils, lack of granules in the cytoplasm, the appearance of ring-shaped nuclei, cytoplasm vacuolization and others.
The combination of data quality and (or) quantitative manifestations myelogram may occur in various diseases, such as anemia, acute and chronic leukemias, myelodysplastic syndrome, Chediak anomaly, myelofibrosis, lymphoma, plasma cell neoplasia, and others.
Fragment myelogram animals lymphocytic leukemia without treatment. Bone marrow hypercellular
To produce quality products using bone marrow cytological centrifuge, which allows you to create microscopic slides with a monolayer of cells.
The study of qualitative and quantitative composition of bile is carried out by HPTLC (high performance thin layer chromatography). It is known that bile acids are able to form conjugates with various amino acids [Huijghebaert S.M., Hoffman A.F., 1986]. So spend the enzymatic hydrolysis of samples [Batta A.K. et al,. 1984; Batta A.K. et al., 1985].
Samples were applied to the plate, eluted dried in warm air stream. To detect bile acids and Cholesterol is carried out post chromatographic derivatization plate. Detection is performed on the scanning plate spectrodensitometer TLC Scanner 3 (Camag, Switzerland) at 380 nm and 540 nm.
To determine the immunogenicity of biological products of various interferon-based laboratory staff have developed and validated method for determining the amount of antibody to human recombinant interferon alfa-2a in the blood plasma of mice by ELISA.
At your request can be developed and validated method of determining the amount of antibodies to a variety of biological preparations.
Western Blot
Scope – the study of the mechanisms of action of drugs
MAP-kinase p38, ERK1/2, JNK1/2
GТPаse: Ras, Rac, Сdc42, RhoA
nuclear factors: NF-kB, AP-1, PPARs
and etc.
The camera for the transfer of proteins on micro-cellulose membrane
Photo micro cellulose membrane after Western Blot
Enzyme analysis
Scope – the study of the mechanisms of action of drugs (non-steroidal anti-inflammatory drugs, statins, and others.)
Dipeptidyl peptidase type 4 (DPP-4)
Сyclooxygenase type 1 and 2 (COX-1/COX-2)
lipoxygenase type 5, 12, 15 (5, 12, 15-LOX)
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase)
Angiotensin-converting enzyme and others.
lots of the speed of the enzymatic reaction of DPP-4 in the presence of a substrate concentration of inhibitor (1) and absence (2) for rat plasma
ELISA
Scope – the study of the pharmacokinetics and mechanisms of action of drugs
IL-1β, IL-2, TNFα, IL-4, IL-6, IL-8, IL-10, IFNs и др.
Muc5AC
Matrix metalloproteinase
Prostaglandins and leukotrienes
The hormones insulin, glucagon
Estrogen, progesterone, testosterone
follicle-stimulating hormone, luteinizing hormone
and many other plasma proteins, serum exudates laboratory animals, supernatants of cell lines
Analysis cytotoxicity on cell lines. MTT-test
Scope – Toxicology
Culture of rat fibroblasts
Human lung carcinoma: A549
Cervical Carcinoma: HeLa
Monocytic leukemia: L41
Acute lymphatic leukemia: THP-1
Histiocytic lymphoma: U937
Analysis cytotoxicity on cell lines
Culture fibroblasts isolated from skin of rat embryos
Photo of fibroblasts in the field of confocal microscopy at an excitation wavelength / absorption of 540/565 nm. The red colored fibrillary actin.
Type 96-well tissue culture plate after MTT test formulation and application of DMSO to the wells
Interaction with Toll-like receptors
Scope – the study of the mechanisms of action of drugs (anti-inflammatory, antiviral) and adjuvant
TLR1/2, TLR4, TLR5, TLR6, TLR 3,7,8,9 cell lines HEK-Blue-hTLRs (InvivoGen, США)
Analysis of interaction with TLR4 cell line HEK-Blue-hTLR4 (InvivoGen, USA)
Using the platform of screening kits LanthaScreen (Thermo Fisher Scientific, USA)
Scope – the study drug mechanisms of action
RAR and RXR – retinoic acid receptors
Steroid hormone receptors (estrogen receptor, progesterone)
Nuclear receptors PPARs (peroxisome proliferator-activated receptors)
Thyroid receptor
Vitamin D receptor, and many others.
Analysis of the interaction with the retinoid X receptor beta. Positive control. 9-cis retinoic acid
Analysis of the degranulation of basophils in the rat RBL-2H3
Scope – the study of pharmacodynamics (membrane-stabilizing action of drugs), and mechanisms of action
Schematic representation of the mechanism of action of the substance 48/80 and ionophore A23187 – inductors degranulation. GPCR-coupled receptors G-protein; GTP – guanazin triphosphate; PLC – phospholipase C; InsP3 – inositol triphosphate; SERCA – calcium ATPase
Analysis of peritoneal macrophage phagocytic activity by the absorption of latex particles conjugated to FITC
Scope – toxicology, study of the pharmacodynamics of drugs (immunomodulatory effect)
Mouse peritoneal macrophages. Absorption latex particles conjugated to the fluorescent label FITC. The transmitted light
Mouse peritoneal macrophages. Absorption latex particles conjugated to the fluorescent label FITC. In fluorescence mode (absorbance 495 nm, emission 517 nm), the increase 100x
Analysis of the proliferative activity of T-and B-mouse spleen lymphocytes to incorporate BrdU label
Scope – toxicology, study of the pharmacodynamics of drugs (immunomodulatory effect)
Isolation of mouse splenocytes of the spleen
DNA-comet test
Scope – the study of the mutagenicity and carcinogenicity
DNA-comets test conditions in vitro cell line A549. Positive control of methyl methanesulfonate 6 mkM. Painting SYBR-Green I.
Using alternative model Danio rerio for toxicological studies
Scope – the study of toxicity, genotoxicity
Larva Danio Rerio. 5 days
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of hematological parameters and establishment of reference intervals in preclinical studies. Part 4: primates. Laboratory Animals for Science. 2025; 3. https://doi.org/10.57034/2618723X-2025-03-07 Abstract. The article is the fourth part of the series devoted to establishing reference intervals for hematological parameters in laboratory animals. The aim of this study was to determine normal values and reference intervals for hematological parameters in cynomolgus macaques and common marmosets. Blood samples were obtained from healthy, mature cynomolgus macaques, 126 males and 105 nulliparous females, and healthy, mature common marmosets, 98 males and 89 nulliparous females. The recorded parameters were analyzed under standardized conditions using generally accepted preanalytical and analytical methods from January to December 2024. The study was conducted in two stages: first, the parameters were analyzed using a hematological analyzer, then microscopic analysis. As a result of the study of animal whole blood samples, the following parameters were measured and analyzed: total number of red blood cells (RBC, 1012/L), hematocrit (HCT, %), hemoglobin concentration (HGB, g/dl), mean corpuscular volume (MCV, pl), mean concentration hemoglobin (MCH, pg), mean corpuscular hemoglobin concentration (MCHC, %), the total number of platelets (PLT, 109/l), the total number of white blood cells (WBC, 109/L), as well as the number of lymphocytes (%), monocytes (%) and granulocytes (%). The following parameters were determined during microscopy: the content of rod-shaped and segmented neutrophils, eosinophils, monocytes, basophils, lymphocytes (%) and reticulocytes (%). During the study, it was found that animals do not have statistically significant gender differences within the species and correlate with the literature data. The ranges of indicators such as the number of red blood cells, platelets, total white blood cells, neutrophils and lymphocytes in the Javan macaque are wider than in humans. At the same time, the concentration of mean corpuscular volume of red blood cells (MCV), mean concentration hemoglobin content in the erythrocyte (MCH) and the number of monocytes are higher in humans. In addition, the shaped elements of the blood of this animal species, such as lymphocytes and neutrophils, have a number of morphological differences from their human counterparts. The ranges of indicators such as the number of red blood cells, hematocrit, hemoglobin, platelet count, total number of white blood cells, lymphocytes and reticulocytes are wider than in humans. At the same time, the concentration of the average volume of red blood cells (MCV), the average hemoglobin content in the erythrocyte (MCH) and the number of neutrophils are higher in humans. The eosinophils of the common marigold also have morphological differences from human eosinophils. The results can be used in interpreting the results of preclinical studies and in implementing animal health monitoring programs [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of hematological parameters and establishment of their reference intervals in preclinical studies. Part 3: minipigs. Laboratory Animals for Science. 2025; 2. https://doi.org/10.57034/2618723X-2025-02-07 Abstract. The report continues a series of articles, the main purpose of which is to establish the reference intervals of the indicators of the general blood test most often used in preclinical studies of laboratory animals. This work is the third part of the cycle and focuses on minipigs. The age and weight of the animals corresponded to puberty — 2–2.5 years, 35–40 kg. The study included males and non-pregnant unborn females, without taking into account the phase of the menstrual cycle. The study was conducted using data obtained from intact animals in 2024 at research and manufacturing company “Home оf Pharmacy”. The analytical part of the study included two stages: at the first stage, blood parameters were evaluated using a hematological analyzer, at the second — the calculation of the leukocyte formula by microscopy. During the analysis of whole blood of animals on a hematological analyzer, the values of the parameters were determined: the total number of erythrocytes, hematocrit, hemoglobin concentration, average volume of erythrocytes, average hemoglobin content in erythrocytes, average hemoglobin concentration in erythrocytes, total platelets, total leukocytes, as well as the number of lymphocytes and granulocytes. During the microscopic analysis, the following indicators were determined: the content of rod-shaped and segmented neutrophils, eosinophils, monocytes, basophils, lymphocytes and reticulocytes. The obtained intervals were compared with literary sources and human-specific values. The calculated ranges of concentrations of the average volume of erythrocytes, the average hemoglobin content in erythrocytes, the number of platelets and reticulocytes turned out to be already literary values, and the ranges of concentrations of hemoglobin, the average concentration of hemoglobin in erythrocytes and the total number of leukocytes were wider than literary analogues. Minipigs, unlike humans, have a higher concentration of erythrocytes, an average concentration of hemoglobin in erythrocytes, the number of platelets, lymphocytes and the total number of leukocytes, and a lower mean of the average volume of erythrocytes, the average hemoglobin content in erythrocytes, the number of neutrophils and eosinophils is also observed. The new calculated reference ranges can be useful as in preclinical and veterinary routine practice for monitoring the health status of minipigs [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of hematological parameters and establishment of reference intervals in preclinical studies. Part 2: order carnivora. Laboratory Animals for Science. 2025; 1. https://doi.org/10.57034/2618723X-2025-01-02 Abstract. Assessment of the qualitative and quantitative composition of blood is an important aspect of monitoring the health of laboratory animals and evaluating the correctness of experiments. For this purpose, a general or hematological analysis is used, which allows you to obtain the necessary data without significant time costs. Hematological analysis includes the determination of the number, percentage, and morphological characteristics of shaped blood elements such as erythrocytes, leukocytes, and platelets. Indices of these elements, pathological cell forms and inclusions are also taken into account. To improve the accuracy of the results obtained in preclinical studies, it is recommended to use our own reference intervals of hematological parameters of healthy animals, taking into account local preanalytical, analytical and postanalytical features of the work. This work is the second part of a series of studies aimed at establishing reference intervals of hematological parameters of healthy laboratory animals, including ferrets, cats and dogs, united under the common name predators (order carnivora). The age of all animals corresponded to puberty, and males and non-pregnant unborn females were included in the study, without taking into account the phase of the menstrual cycle. The study was conducted using data obtained from intact animals in the period from January to August 2024 at research and manufacturing company “Home оf Pharmacy”. The study was divided into two stages: assessment of indicators using a hematological analyzer and calculation of the leukocyte formula using microscopic analysis. During the hematological analysis of whole blood of animals, the following parameters were determined: the total number of erythrocytes, hematocrit, hemoglobin concentration, average volume of erythrocytes, average hemoglobin content in erythrocytes, average hemoglobin concentration in erythrocytes, total platelets, total leukocytes, as well as the number of lymphocytes and granulocytes. When calculating the leukocyte formula, the following indicators were determined: the content of rod-shaped and segmented neutrophils, eosinophils, monocytes, basophils and lymphocytes. The obtained intervals were compared with data from literary sources and values typical for humans. The discrepancies between the calculated values and the literature data are due to differences in the parameters of erythrocyte indices, as well as in the number of platelets, leukocytes, neutrophils, lymphocytes, eosinophils and reticulocytes. During the study, reference ranges were identified that can become a valuable tool for tracking the health status of laboratory animals during preclinical studies. These data will contribute to improving the quality and accuracy of the experiments conducted, as well as improving the safety and welfare of animals [Full text is available in Russian].
- Miroshnikov M.V., Kovaleva M.A., Sultanova K.T., Makarova M.N. Variability of hematological blood parameters and establishment of reference intervals in preclinical studies. Part 1: rodents and rabbits. Laboratory Animals for Science. 2024; 4. https://doi.org/10.57034/2618723X-2024-04-04 Abstract. Hematological analysis or a general blood test aimed at assessing the qualitative and quantitative composition of blood allows you to take into account a wide range of indicators. This is one of the most basic and commonly used methods for monitoring the health of laboratory animals and evaluating the progress of an experiment. With its help, you can get a characteristic of all the shaped elements of the blood: erythrocytes, leukocytes and platelets, evaluate their percentage, shape and appearance, detect pathological forms of cells, progenitor cells or various inclusions. This type of analysis can help detect early changes in the body’s health status and identify conditions such as anemia, polycythemia, thrombocytopenia, and leukopenia, which can be symptoms of disease or independent pathologies. That is why it is necessary to have reference intervals of hematological blood parameters of healthy laboratory animals in each scientific center, taking into account critical preanalytical, analytical and postanalytical features. The aim of this study was to determine the reference ranges of hematological blood parameters for both male and female mice, gerbils, hamsters, rats, guinea pigs, and rabbits, which are commonly used as test models in biomedical research. The age of all animals corresponded to the range of puberty, males and non-pregnant and unborn females were included in the study, without taking into account the phase of the menstrual cycle. The data used in this work were obtained from intact animals during the time period January-June of 2024 at research and manufacturing company “Home оf Pharmacy”. The work was divided into two stages: assessing indicators on a hematology analyzer and calculating the leukocyte formula through microscopic analysis. In the whole blood of animals, such indicators were recorded using a hematological analyzer as: total number of erythrocytes, hematocrit, hemoglobin concentration, average volume of erythrocytes in the total volume of the sample, average hemoglobin content in erythrocytes, average concentration of hemoglobin in erythrocytes, total number of platelets, total number of leukocytes, number of lymphocytes and granulocytes. When calculating the leukocyte formula, such indicators as the content of neutrophils, eosinophils, monocytes, basophils and lymphocytes were recorded. When comparing the obtained intervals with reference values from literary sources, it was shown that, in general, the ranges of the considered indicators are similar, but there are also differences. The greatest differences were associated with the number of erythrocytes, platelets, monocytes, lymphocytes, neutrophils and hemoglobin concentration. The reference intervals calculated during the study can be a useful tool for monitoring the health status of laboratory animals during preclinical experiments [Full text is available in Russian].
- Miroshnikov M.V., Kovaleva M.A., Sultanova K.T. Review of methods for determining the glomerular filtration rate in preclinical studies. Laboratory Animals for Science. 2024; 3. https://doi.org/10.57034/2618723X-2024-03-06 Abstract. The potential risk of nephrotoxic effects is an important aspect that should be considered already at the preclinical stage of drug development. Exposure of the kidneys to toxic doses of investigational substances may be accompanied by cell damage primarily due to high blood flow in the kidney, clearance as well as metabolism of xenobiotics. Glomerular filtration rate (GBR) is one of the indicators of the functional state of the urinary system. A descriptive analysis of scientific literature summarizing the methods of GBR determination most commonly used in preclinical studies in different types of laboratory animals was performed. The factors influencing its determination were revealed. The values of GBR in laboratory animals at its determination by different methods are systematized. animals at its determination by different methods. The research was done using PubMed and Google Scholar databases. The review included available publications as of March 12, 2024. It has been shown that GBR can be one of the methods for assessing the risk of possible nephrotoxic effects of a drug. GBR is determined using endogenous and exogenous markers, which have several advantages and disadvantages. According to the literature, the most commonly commonly used markers for estimation of GBR are inulin (exogenous marker) and endogenous creatinine. The choice of the most optimal marker should be made in the context of each individual preclinical study [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 11: dogs. Laboratory Animals for Science. 2023; 4. https://doi.org/10.57034/2618723X-2023-04-02Abstract. Dogs are a common in vivo test system in preclinical studies due to the relatively large body size sufficient for surgical manipulations, as well as the pathophysiology of various diseases similar to humans. A separate point of application of the animal species in question in preclinical studies is the study and therapy of oncological diseases. The aim of the work was to create its own database of reference intervals of biochemical blood parameters of Beagle dogs. These norms are necessary in preclinical studies when assessing the state of animal health, monitoring the formed pathological model, as well as checking the safety of the studied drugs. Biological samples used for the formation of reference intervals were obtained from intact animals in research and manufacturing company “Home оf Pharmacy”. All manipulations and experiments carried out were approved by the bioethical commission. The study included 56 males and 48 females. The age of the animals corresponded to the range of 10–18 months, the body weight of females was 7–11 kg, and males 8–14 kg. In order to implement a uniform approach when creating reference intervals, all manipulations were carried out under the same conditions. For the study, blood was used, which was taken from the lateral subcutaneous vein of the leg of the studied animals on an empty stomach, without sedation and anesthesia. The following parameters were recorded in the blood serum of animals: creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose, creatine kinase, lactate dehydrogenase and total bilirubin, the albumin-globulin coefficient was calculated. Statistical outliers were estimated using the Tukey method, the type of distribution was determined using the Shapiro—Wilk criterion, paired comparisons between animals of different sexes were carried out using the Mann—Whitney U-test and the Student t-test. The obtained ranges of values of males and females correlated with each other for all the considered indicators, no statistical difference was revealed. When comparing the obtained intervals with the reference ranges of dogs from other literature sources, it was shown that, in general, the ranges of the considered indicators are similar, but there are also differences that can be explained by a wide list of factors. These include the image of keeping animals, as well as the preanalytical and analytical stages of the study. A comparative analysis of the interindividual variability of the biochemical parameters of the blood of dogs and humans showed the presence of some species differences that need to be taken into account in experimental activities [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 10: mongolian gerbils. Laboratory Animals for Science. 2023; 3. https://doi.org/10.57034/2618723X-2023-03-06 Abstract. Gerbils as a type of laboratory animals are widely used as experimental models in a number of areas of biomedical research. This type of laboratory animals is relatively easy to maintain and handle. They are an alternative test system among rodents such as mice and rats. They are most often used in the study of cerebral ischemia or stroke, behavioral research, aging processes, the development of oncological diseases, as well as the study of parasitic, viral and bacterial infections, studies of the mechanisms and therapy of epileptic seizures and metabolic disorders such as obesity and diabetes mellitus. The aim of this work was to create a database of reference intervals of biochemical parameters of normal healthy mature Mongolian gerbils with further use in daily routine laboratory practice in preclinical centers. The data that were used to form the reference intervals were obtained from intact animals in “Home оf Pharmacy”. All manipulations and experiments were approved by the bioethical commission. The study involved 20 males and 20 females (non-pregnant excluding the estrous cycle phase) of Mongolian gerbils. The age of the animals corresponded to the range of 6–8 weeks, the body weight of males and females was within 60 g. The levels of the following parameters were determined in the blood serum of animals: creatinine, urea, alanine aminotransferase, aspartateaminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose, total bilirubin, the number of globulins was calculated, as well as the ratio of albumin/globulins. The obtained ranges of males and females had no statistical difference between them. These intervals were analyzed for comparison with other reference intervals of gerbils found in the scientific literature, as well as with ranges of similar indicators characteristic of humans. Norms of biochemical parameters of blood serum of gerbils are an important tool necessary for monitoring animal health during biomedical research, monitoring the dynamics of modeling pathological conditions in animals and studying the safety of new pharmacological agents. An important aspect in preclinical research is the creation of any reference intervals of laboratory animals in each scientific center separately. This is due to a large number of pre-analytical, analytical and post-analytical features, as well as minimizing the risk of misinterpretation of the data obtained during biomedical research [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 8: syrian hamsters. Laboratory Animals for Science. 2023; 2. https://doi.org/10.57034/2618723X-2023-02-08 Abstract. Biochemical parameters of blood serum are important parameters for assessing the health of laboratory animals. The Syrian Hamster is a widely used test system in animal experiments. They have unique anatomical and physiological features, such as optimal body size, large cheek sac, high reproduction rate and short life cycle, which together makes hamsters a convenient test system used in preclinical studies. This type of animal is used not only in the study of toxicological properties and assessment of pharmacological safety, but is also involved in various pharmacodynamic studies as a model organism for studying a wide range of pathological conditions associated with the immune response, respiratory system, carcinogenesis, metabolic disorders. During the study, reference intervals of the main biochemical parameters of the blood of Syrian hamsters were established. This procedure is necessary for an adequate understanding of the condition of animals in the experiment, assessment of the toxicity and safety of new pharmacological substances, control of the formation of model pathologies and evaluation of the effectiveness of pharmacological agents. The values used for the formation of reference intervals were obtained from intact animals for the time period June–December 2022 in Research and manufacturing company “Home оf Pharmacy”. The study included biological samples of 30 males and 30 females of Syrian hamsters. The age of the animals corresponded to the range of 6–8 weeks, the body weight of males and females was in the range of 100–115 grams. The study was carried out in compliance with the principles of the European Convention for the Protection of Vertebrates Used for Experiments and Other Scientific Purposes and in accordance with the rules of good laboratory practice. The determination of the biochemical parameters of interest was carried out under the same conditions using generally accepted preanalytical and analytical methods. Blood sampling from animals was performed using a cardiac puncture. The following parameters were registered in animal serum: creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, globulins, albumin/globulin ratio, glucose, total bilirubin. The obtained reference ranges of biochemical parameters were generally similar to the published data. Differences were found in urea, alkaline phosphatase, alanineaminotransferase, aspartateaminotransferase and glucose — the values were higher than the literature data. For an adequate interpretation of the experimental values obtained, an important aspect in preclinical studies is the establishment of intralaboratory reference intervals for the biochemical blood values of healthy animals in each research laboratory. This is due to the preanalytical and analytical characteristics of the analysis, the breed of animals and the conditions in which they are housed [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies Part 9: cats. Laboratory Animals for Science. 2023; 1. https://doi.org/10.57034/2618723X-2023-01-03 Abstract. The etiopathogenesis of many diseases and pathological conditions of cats and humans is largely similar to each other. These include leukemia, Alzheimer’s disease, cardiovascular diseases, infections, immunodeficiency conditions, obesity, diabetes mellitus and retinal pathology. In view of this, the cat can be a model of choice in preclinical studies for the study of these diseases, the development of new methods of surgical correction, as well as testing new pharmacological substances. Due to the widespread involvement of cats in preclinical studies, there is a problem of monitoring the normal state of the body and registering the flow of vital processes. Biochemical analysis of blood serum of laboratory animals is a routine part of preclinical centers, which is an integral part of the assessment of the state of the body. As a rule, the obtained values are interpreted by comparison with the reference interval. The reference interval or range of norm in preclinical studies is an interval of values that is considered a physiological norm. The reference interval or range of norm in preclinical studies is an interval of values that is considered a physiological norm. This is the basis, the starting point for the researcher when interpreting the obtained set of results and further determining the presence or absence of a pathological process in laboratory animals. The purpose of this work was to establish the main biochemical parameters in the blood serum of cats of the Russian blue breed. The data used for the formation of reference intervals were obtained from intact animals for the time period May–November 2022 in “Home оf Pharmacy”. The study included 30 males and 28 females of cats. The age of the animals corresponded to the range of 6–12 months. In the blood serum of animals, such indicators as creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose, creatine kinase, lactate dehydrogenase and total bilirubin were recorded. When comparing the obtained intervals with reference values from literary sources, it was shown that, in general, the ranges of the considered indicators are similar. When comparing the obtained reference intervals of biochemical parameters of the blood of cats and the corresponding reference intervals of humans, it was concluded that the upper limit of such indicators as creatinine, urea, aspartate aminotransferase, alanine aminotransferase, globulins, creatine kinase, glucose (females) and lactate dehydrogenase is higher in laboratory animals. The upper limit of cholesterol, triglycerides, albumin, the ratio of albumins to globulins and total bilirubin is lower in cats than in humans. The reference intervals of biochemical blood parameters of Russian blue cats established in the study are a useful tool in the field of preclinical research and can be used to monitor animal health, the adequacy of the formed pathological model and study the toxicological properties of new drugs [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Akimova M.A., Makarova M.N. Determination of reference intervals of creatinine clearance in laboratory animals. Laboratory Animals for Science. 2022; 4. https://doi.org/10.57034/2618723X-2022-04-03 Abstract. The assessment of renal function is an important part of monitoring the health of laboratory animals in preclinical studies. One of the most important indicators for the assessment of renal function is serum creatinine concentration and endogenous creatinine clearance. Creatinine is the breakdown product of creatine phosphate in muscle tissue, which is further filtered from the blood by the kidneys and excreted in the urine. Its level depends on the amount of muscle mass and the intensity of the animals metabolic processes. In general, an increase in creatinine levels in the blood reflects insufficient renal filtration ability, it is worth noting that creatinine concentration is not a specific marker of nephropathies, making its single use in the assessment of renal dysfunction incorrect. One of the indicators to monitor animal health as well as renal excretory dysfunction is endogenous creatinine clearance, which reflects the level of glomerular filtration. A review of the literature has shown that information on endogenous creatinine clearance in laboratory animals is insufficient and the data vary widely between animal species and between lines of the same animal species. A review of the literature has shown that information on endogenous creatinine clearance in laboratory animals is insufficient and the data vary widely between animal species and between lines of the same animal species. The aim of the study was to establish a base of reference intervals of creatinine clearance in laboratory animals — CD-1 mice, Mongolian gerbils, Syrian hamsters, Wistar rats, Agouti guinea pigs, ferrets, cats, Beagle dogs, minipigs, rabbits, Javanese macaques and marmoset. In the course of the work, a method of obtaining urine samples within 24 hours using metabolic cells was perfected. Urine collection in large animals was carried out using a hydrophobic bedding. Creatinine clearance was determined for all animals under the same conditions using common analytical methods. The endogenous creatinine clearance values of laboratory animals established in this work may be useful in the evaluation of nephrotoxicity within the framework of pharmacological safety, in the study of the pharmacological potential of new nephrotherapeutic agents, and in the monitoring of animal health [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 7: guinea pig. Laboratory Animals for Science. 2022; 3. https://doi.org/10.57034/2618723X-2022-03-01 Abstract. The guinea pig is a significant model in preclinical studies because of its optimal body size, wide commercial availability; similarity to humans in anatomical, immunological and biochemical features. The animals in question are widely used for research in allergology and immunology, infectious and cardiovascular diseases, atherosclerosis, and arthritis. In addition, guinea pig metabolism of lipids, cholesterol and glucose is similar to that of humans. Due to the high involvement of these animals in preclinical studies and the possibility of modeling a large number of pathological conditions, an important point is to monitor animal health, assess the condition of internal organs and information on metabolism — the metabolism of lipids, proteins and carbohydrates. The aim of this study was to establish the reference intervals of some biochemical parameters of guinea pig blood serum. These parameters are required in preclinical studies for monitoring animal health, assessing the presence/absence of drift of the studied parameters, comparing the obtained values with human values, and evaluating model pathology. To form the reference intervals we used data obtained from intact healthy animals in December 2021 — April 2022 at «Home оf Pharmacy». All experiments performed were approved by the bioethics commission. The following parameters were determined in the blood serum of the animals on an automatic biochemical analyzer Rendom Access A-25 using appropriate test kits: creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, high-density lipoproteins, α-amylase, triglycerides, total protein, albumin, glucose, creatine kinase, lactate dehydrogenase and total bilirubin. Based on the total protein content of each animal, the number of globulins was determined and the guinea pig albumin/globulin ratio was calculated. When comparing the obtained and literature data, it was shown that the calculated in the «Home оf Pharmacy» reference values of biochemical parameters of animals in general correlate with those of other research centers and laboratories, which confirms their representativeness. When comparing the obtained values of biochemical blood parameters of guinea pigs with human data, it was shown that some values are similar to each other — creatinine, lactate dehydrogenase, globulins. Alkaline phosphatase, cholesterol, high-density lipoproteins, α-amylase, triglycerides, total bilirubin and glucose differ in the value of the reference range. Urea, alanine aminotransferase and aspartate aminotransferase were higher in animals than in humans. These differences need to be taken into account in further preclinical studies for a more accurate analysis of the results obtained [Full text is available in Russian].
- Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 6: Macaca fascicularis. Laboratory Animals for Science. 2022; 2. https://doi.org/10.29296/2618723X-2022-02-02 Abstract. Despite numerous attempts to find alternative models to evaluate the efficacy and safety of drugs, it is currently impossible to completely abandon research on large laboratory animals. Macaca fascicularis play an important role in preclinical studies in the study of vaccines, the development of pharmaceuticals, and toxicological studies. Genetic proximity to humans causes the similarity of the two species according to physiological and biochemical criteria, the pathogenesis of certain diseases and the mechanism of action of various chemicals on the body. These animals are susceptible to age-related pathologies characteristic of humans, such as cardiovascular diseases, behavioral disorders, Alzheimer’s disease, obesity, type 2 diabetes mellitus. The use of cynomolgus macaque in preclinical studies mediates the need for laboratory control of the internal state of animals. The paper reviewed and analyzed the reference values of some biochemical parameters of the blood of Macaca fascicularis. To form the intervals, we used data obtained from intact animals on the basis of research and manufacturing company «Home оf Pharmacy». The normal ranges of such parameters as creatinine, urea, aspartate aminotransferase, alanine aminotransferase, cholesterol, triglycerides, total protein, albumin, globulins, albumin/globulin ratio, glucose, lactate dehydrogenase and creatine kinase obtained during the work were comparable between male and female primates. The exception is alkaline phosphatase — the reference range of the indicator under consideration in males was much wider than in females. When comparing the reference intervals obtained at «Home оf Pharmacy» with the intervals of Macaca fascicularis from literary sources, it is shown that, in general, the ranges of the indicators under consideration are comparable, but there are also differences that may be caused by animal stress, methods of processing and blood sampling, nutrition, climate, conditions of detention and age. The obtained reference ranges of biochemical blood parameters of cynomolgus macaque are necessary in preclinical studies to create a high-quality basis for future experimental studies using Macaca fascicularis, more accurate analysis of the information obtained and monitoring of animal health.
- Voitenko N.G, Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 3: mini pigs. Laboratory Animals for Science. – 2020, №3. https://doi.org/10.29296/2618723X-2020-03-02 Abstract. For today, scientists have more than a dozen other laboratory animals at their disposal to conduct toxicological, pharmacokinetic and other studies in addition to rodents. Pigs have been used for a long time to study organ and tissue transplants and surgical training for medical students, but their use can be much broader. The anatomical similarity to humans and the large size of these animals allow us to successfully conduct studies of the cardiovascular, digestive and urinary systems, as well as use them in preclinical and Toxicological studies. In this regard, the establishment of reference intervals of biochemical blood parameters of laboratory pigs is an urgent task. Our article presents reference intrevals of biochemical parameters of blood of dwarf pigs obtained using the classical approach. We used the results of biochemical blood analysis of 15 males and 15 females of clinically healthy dwarf pigs aged 9-11 months, weighing 14-26 kg, raised in our nursery. In addition to the main biochemical parameters (creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose, and total bilirubin), additional parameters are presented – an expanded lipid profile, calcium and phosphorus concentrations, and the activity of a number of enzymes (lactate dehydrogenase, creatine kinase, amylase, gamma-glutamyltransferase, and cholinesterases), which are biochemical markers of damage to various systems and organs. The most pronounced differences were found in the study of the lipid profile of male and female dwarf pigs: the concentration of total cholesterol and triglycerides in the blood of females was higher on average by 1.5 and 2 times, respectively. In addition, the concentration of low-density lipoprotein cholesterol in the blood serum of females was on average 1.8 times higher than in the blood serum of males. Less pronounced but statistically significant differences were found in the concentration of total protein and globulins. The analysis of the presented reference intervals with the literature data showed the comparability of the obtained values. Despite the significant similarity of the biochemical profiles of humans and laboratory pigs, it is necessary to take into account the presence of species differences when considering the results of preclinical studies [Full text is available in Russian].
- Voitenko N.G., Makarova M.N., Kovaleva M.A. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 2: rabbit. Laboratory Animals for Science. – 2020, №2. https://doi.org/10.29296/2618723X-2020-02-01 Abstract. The data of the biochemical analysis are the reference for most of the preclinical studies. The establishment and revision of reference ranges of biochemical indicators for all types of used laboratory animals is an important task for each testing center. In the Russian Federation, rabbits are widely used for various studies, for example, the study of the general toxic properties of original drugs, or long-acting drugs, the study of the specific activity of drugs used for the treatment of the visual organs and the musculoskeletal system, etc. Despite the sufficient study of the species as a whole, Russian periodicals present a limited amount of data on the reference intervals of biochemical indicators. Our test center has accumulated a data bank of such indicators that were determined in multiple-dose toxicity studies, which allowed us to conduct a retrospective analysis and review the available reference intervals. The calculation was based on observation data obtained in the period from January 2018 to December 2019. The determination of biochemical parameters in this period of time was carried out on the same equipment using the same methods. A retrospective analysis of the data was performed on 13 biochemical parameters of blood serum of three breeds of rabbits – New Zealand, chinchilla, white giant. The sample consisted of 127 females and 127 males, the age of the animals in the studies was 16-25 weeks (the weight of the animals was 3-5 kg). The article presents reference intervals for creatinine, urea, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, globulin, glucose, total bilirubin, and the albumin/globulin ratio. The necessity of creating intra-laboratory databases of reference intervals in each test center is justified. Interindividual variability was calculated for the specified biochemical parameters. The greatest inter-individual variability (more than 30%) was found for such indicators as alkaline phosphatase, triglycerides, cholesterol and total bilirubin. The use of retrospective data analysis allows us to implement the principles of 3Rs and get more correct data on a larger sample of laboratory animals. The analysis of the reference intervals obtained by us in comparison with the literature data, in general, showed their comparability, which can be considered as an additional confirmation of the satisfaction of the established intra-laboratory standards [Full text is available in Russian].
- Горячева М.А., Крышень К.Л., Кательникова А.Е., Акулова Е.Г., Макарова М.Н., Макаров В.Г. Методические аспекты использования базофилов крысы линии RBL-2H3 для изучения дегрануляции // Молекулярная медицина.– 2016. –Т. 14, № 3. – С.48-52.
- Косман В.М., Крышен ьК.Л., Крышень А.А., Гаврилин М.В., Пожарицкая О.Н., Макарова М.Н. Валидация теста «Аномальная токсичность» для стандартизации субстанции инсулина // Разработка и регистрация лекарственных средств. – 2016, № 3. – С. 138-144.
- Faustova N.M., Kosman V.M., Pozharitskaya O.N. Preliminary study of chemical composition and dipeptidyl peptidase IV inhibitory activity of various extracts of Larix sibiricain vitro Abstracts. Phitopharm. 2016. Obzory po klinicheskoj farmacologii i lekarstvennoj terapii. – 2016. – Vol. 14. – P. 17-18.PRELIMINARY STUDY OF CHEMICAL COMPOSITION AND DIPEPTIDYL PEPTIDASE IV INHIBITORY ACTIVITY OF VARIOUS EXTRACTS OF LARIX SIBIRICA IN VITRO
- Фаустова Н.М., Ушакова Н.В., Макарова М.Н., Макаров В.Г. Особенности ферментного спектра пищеварительного тракта лабораторных животных и человека // Международный вестник ветеринарии. -2016, № 2. –С. 125-146.Особенности ферментного спектра пищев. тракта лаб. животных и человека
- Obluchinskaya E.D., Маkarova M.N., Pozharitskaya O.N., Shikov A.N. Effects of ultrasound treatment on the chemical composition and anticoagulant properties of dry Fucus extract // Pharmaceutical Chemistry Jornal. -2015. –Vol. 49, № 3. –P. 183-186.
- Облучинская Е.Д., Макарова М.Н., Пожарицкая О.Н., Шиков А.Н. Влияние ультразвуковой обработки на химический состав и антикоагулянтные свойства сухого экстракта фикуса // Химико-фармацевтический журнал. -2015. –Т. 49, № 3. –С. 61-64.
- Pozharitskaya O.N., Shikov A.N., Kosman V.M., Selezneva A.I., Urakova I.N., Маkarova M.N., Makarov V.G. Immunomodulatory and antioxidants properties of fixed combination of fish oil with plant extracts // Synergy. -2015. №2. –P. 19-24.
- Крышень К.Л., Фаустова Н.М., Пожарицкая О.Н., Шиков А.Н., Макарова М.Н., Макаров В.Г. Механизм противовоспалительного действия комплекса, выделенного из печени трески. Ингибирование ЦОГ-2 и 5-ЛОГ. Сообщение №2. // Международный вестник ветеринарии. -2014, №1. –С. 80-84. Механизм противовоспалительного действия комплекса, выделенного из печени трески. Ингибирование ЦОГ-2 и 5-ЛОГ
- Патент RU 2493861 C1 Авторы: Пожарицкая О.Н., Демченко Д.В., Шиков А.Н., Макарова М.Н., Макаров В.Г. Биологически активный комплекс, обладающий противоаллергическим действием. Опубликовано 27.09.2013. Бюл. № 7.
- Патент RU 2488402 C1 Авторы: Иванова С.А., Пожарицкая О.Н., Шиков А.Н., Макарова М.Н., Макаров В.Г. Средство, обладающее противовоспалительным и противоаллергическим действием. Опубликовано 27.07.2013. Бюл. № 21.
- Kovaleva M.A., Kokareva M.N., Makarova M.N., Pozharitskaya O.N., Makarov V.G. Antioxidant activity of the green sea urchin (Strongylocentrotus drobachiensis) gonads extract on the model of streptozotocin (STZ)-diabetic mice // The 17th international congress. Phytophrm, 2013. Vienna, Austria, 8-10 July 2013. Обзоры по клинической фармакологии и лекарственной терапии. –Т. 11. –С. 56.
- Ковалева М.А., Иванова С.А., Макарова М.Н., Пожарицкая О.Н., Шиков А.Н., Макаров В.Г. Влияние комплексного препарата из панциря морских ежей на концентрацию глюкозы в крови и параметры окислительного стресса на модели сахарного диабета II типа / М.А. Ковалева [и др.] // Экспериментальная и клиническая фармакология. – 2013. – Т. 76, № 8. – С. 27-30.
- Pozharitskaya O.N., Shikov A.N., Makarova M.N., Ivanova S.A., Kosman V.M., Makarov V.G., Bazgier V., Berka K., Otyepka M., Ulrichova J. Antiallergic effects of pigments isolated from Green sea urchin (Strongylocentrotus droebachiensis) shells // Planta Med. -2013. –Vol. 79. –P. 1698-1704.
- Крышень К.Л., Демченко Д.В., Шиков А.Н., Пожарицкая О.Н., Макарова М.Н., Макаров В.Г. К механизму противовоспалительного действия комплекса, выделенного из печени трески. Антиэкссудативное действие. (Сообщение 1). // Международный вестник ветеринарии. -2013, №4. –С. 100-105. К механизму противовоспалительного действия комплекса, выделенного из печени трески. Антиэкссудативное действие
- Кашкин В.А., Соколова А.В., Абрашова Т.В., Макарова М.Н., Макаров В.Г. Особенности гемостаза у крыс// Международный вестник ветеринарии. -2013, №4. –С. 88-93. Особенности состояния гемостаза у крыс
- Справочник Физиологические, биохимические и биометрические показатели нормы экспериментальных животных. Под ред.: д.м.н. Макарова В.Г., д.м.н. Макаровой М.Н. Абрашова Т.В., Гущин Я.А., Ковалева М.А., Рыбакова А.В., Селезнева А.И., Соколова А.П., Ходько С.В. СПб.: Из-во «ЛЕМА», 2013. -116 с. СПРАВОЧНИК. Физиологические, биохимические и биометрические показатели нормы экспериментальных животных
- Селезнева А.И., Макаров В.Г., Дьячук Г.И., Забозлаев А.А., Макарова М.Н., Ходько С.В., Ковалева М.А. Противоишемические свойства нового антиоксидантного препарата Валеокор-Q10 (экспериментальное исследование) // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 168.
- Крышень К.Л., Ацапкина А.А., Рыбакова А.В., Демченко Д.В., Рыдловская А.В., Пожарицкая О.Н., Макарова М.Н., Макаров В.Г. Двойной селективный ингибитор циклооксигеназы-2 и 5-липооксигеназы природного происхождения // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 105.
- Ковалева М.А., Селезнева А.И., Макарова М.Н., Иванова С.А., Пожарицкая О.Н. Экспериментальная оценка гипогликемической и антиоксидантной активности препаратов на основе природных хинонов // Материалы IV съезда фармакологов России «Инновации в современной фармакологии». 18-21 сентября 2012 г., республика Татарстан, г. Казань. –М.: 2012. –С. 89.
- Крышень К.Л., Рыбакова А.В., Рыдловская А.В., Макарова М.Н., Дадали В.А., Макаров В.Г. Биохимические основы противовоспалительного действия нового полипептидного комплекса, полученного из печени трески // Материалы всероссийской молодежной конференции «Фармакологическая коррекция процессов жизнедеятельности. Доклинические и клинические исследования новых лекарственных препаратов» г. Уфа, 8-10 июля 2012 г. – С. 92-94.
- Крышень К.Л., Демченко Д.В., Рыбакова А.В., Дадали В.А., Рыдловская А.В., Пожарицкая О.Н., Макарова М.Н., Шиков А.Н., Макаров В.Г. Оценка противоаллергенных свойств нового полипептидного препарата из печени тресковых // Экспериментальная и клиническая дерматокосметология. -2012, № 2. –С. 38-42.
- Kryshen K.L., Demchenko D.V., Ribakova A.V., Rydlovskaya A.V., Atsapkina A.A, Beketova D.V., Pozharitskaya O.N, Makarova M.N., Dadali V.A., Makarov V.G Biochemical basis of antiiflamatory properties of peptide complex obtained from the cod liver (Cadidae) // Abstracts. 2012. Obzory po klinicheskoj farmacologii i lekarstvennoj terapii. -2012. –Vol. 10, № 2. –M73.
- Ковалева М.А., Макарова М.Н., Иванова С.А. Изучение сахароснижающего и антиоксидантного действия комплекса полигидроксинафтохиноновых пигментов из панциря морских ежей на модели экспериментального стрептозотоцин-индуцированного диабета // Современные проблемы медицинских и фармацевтических наук: Сборник материалов международной научно-практической конференции. –Днепропетровск: Организация научных медицинских достижений «Salutem», 2012. –С. 42-44.
- Obukhova V.V., Selezneva A.I., Makarova M.N., Khodko S.V. An investigation of the anti-oxidant activity of herbal mixtures on an experimental hyperlipidemia model in wistar rats // Fhytopharm. 2011. 15th International congress. Book of abstracts. Nuremberg.Germany 25-27 July 2011. P.81-82
- Obukhova V.V., Ivanova S.A., Makarova M.N., Khodko S.V. An investigation of the herbal mixtures influence on the bile composition in a rabbit experimental atherosclerosis model // Fhytopharm. 2011. 15th International congress. Book of abstracts. Nuremberg.Germany 25-27 July 2011. P.80-81
- Kryshen K.L., Atsapkina A.A., Akulova E.G., Rynchukovsky M.S., Makarova M.N., Pozharitskaya O.N., Shikov A.N., Makarov V.G., Dadali V.A. Anti-inflammatory effects of two peat distillates on the model of carrageenan air pouch in the rat. // Fhytopharm. 2011. 15th International congress. Book of abstracts. Nuremberg.Germany 25-27 July 2011. P.70-71
- Крышень К.Л., Дадали В.А., Бейшебаева Ч.Р., Павлова Р.Н., Смертина М.Н., Макарова М.Н., Карякина Л.А. Исследование взаимодействия диаллилдисульфида и омегалицина с ретиноидными рецепторами // Hi-Tech. Сборник статей под ред. А.П. Кудинова, Том 4, Санкт-Петербург, 2011 С.224-225.
- Макарова М.Н., Макаров В.Г. Молекулярная биология флавоноидов (Химия, биохимия, фармакология). Руководство для врачей // СПб., СПб., из-во «Лема» 2010 г. С. 428.
- Абрашова Т.В., Соколова А.П., Селезнева А.И., Хуттунен О.Э., Макарова М.Н., Макаров В.Г. Вариабельность биохимических и гематологических показателей у лабораторных крыс в зависимости от линии возраста // Международный вестник ветеринарии. – 2010, №2 С.55-60.
- Соколова А.П., Абрашова Т.В., Хуттунен О.Э., Селезнева А.И., Макарова М.Н., Макаров В.Г. Сравнительная характеристика биохимических и гематологических показателей у лабораторных крыс разных линий и возрастов // Международный вестник ветеринарии. – 2010, №2 С.58-62.
- Guseva S.I., Shikov A.N., Pozharitskaya O.N., Krishen K.L., Makarov V.G., Makarova M.N. Anti-inflammatory effect of tablets with Salvia extract using carrageenan air pouch model // Book of abstracts of the 57 th Interregional Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research. August 16-20, 2009, Geneva. Switzerland, 2009 P.7
- Abrashova T.V., Sokolova A.P., Avdeeva O.I., Karachinskaya I.V. Effects of two different medicinal forms of ascorbic acid on urine samples composition // Fhytopharm. 2009. 13 th International congress. Book of abstracts. Leiden. Netherlands. 29-31 July 2009. P. 77
- Крышень К.Л., Гусева С.И., Тесакова С.В., Ацапкина А.А., Макарова М.Н., Шиков А.Н., Макаров В.Г., Дьячук Г.И. Оценка противовоспалительного действия лекарственных препаратов на основе шалфея // Цитокины и воспаление 2009. Т.8, № 4. С.67-72.
- Зенкевич И.Г., Ищенко Е.В., Макаров В.Г., Макарова М.Н., Селезнева А.И. Новые примеры участия кислорода воздуха в химических реакциях в растворах // Журнал общей химии. -2008. –Т. 78, вып. 9. –С. 1449-1456.
- Zhorina A.S., Makarova M.N. Experimental study of reducing activity of cytochrpome-c // Fhytopharm. 2007. 11 th International congress. Book of abstracts. Leiden. Netherlands. 27-30 June 2007. P.156.
- Макаров В.Г., Макарова М.Н., Смирнов Л.Д., Буданов С.В., Пахомов В.П., Демченкова Е.Ю., Онацкий Н.М. Методические указания по изучению антиоксидантной активности фармакологических веществ // Ведомости НЦ ЭСМП. -2007, № 2. –С. 96-103.
- Жорина А.С., Селезнева А.И., Макарова М.Н., Макаров В.Г. Про – и антиоксидантные свойства биоантиоксидантов в модельных условиях // Биоантиоксидант. VII Международная конференция. 25-26 октября 2006 г., Москва. – М.: Из-во РУДН, 2006. С. 130-132.
- Tikchonov V.P. Rydlovskaya A.V., Makarov V.G., Makarova M.N., Pozharitskaya О.N. Investigation of anti- inflammatory activity of complex herbal oil extract in vitro and in vivo // Abstracts 54 th annual congres on medicinal plant research. 29 august-2 september 2006 // Planta Medica.-2006. – Vol.72 P.1007-1008.
- Tikchonov V.P., Ridlovskaa A.V., Makarova M.N., Makarov V.G Investigation of anti- inflammatory activity of complex herbal oil extract in vitro and in vivo // GA. 54th Annual Congress on Medicinal Plant research. 2- august – 2 september 2006, Helsinki. Finland. Planta Medica.-2006. – Vol.72, № 11. P.107.
- Makarova M.N., Zhorina A.S., Selezneva A.I. The study of antioxidant properties of some plant compounds/flavonoids in system with generation of superoxide and peroxil radicals // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2006, 27-30 июня: Матер. X международного съезда. – Санкт-Петербург, Россия. – 2006. С.548-549.
- Makarova M.N.,Tesakova S.V., Eshenko A.Yu.,Siivari J., Galambosi B., Zenkevich I.G. Study of antiradical activity of Bergenia ssp. Leave samples in vitro // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2006, 27-30 июня: Матер. X международного съезда. – Санкт-Петербург, Россия. – 2006. С. 488-493
- Makarova M.N., Makarov V.G., Selezneva A.I. Anti-and prooxidant effect of flavonoids and their regulatory role in cell function // VIII World Congress: International society for adaptive medicine (ISAM). Moscow, Russia, June 21-24, 2006. P.179.
- Makarova M.N., Pozharitskaya О.N., Shikov A.N., Rydlovskaya A.V., Makarov V.G. Fractions from Vaccinium myrtillus L. fruits in combinations with carotenoids: Study of free radical scavenger properties in vitro // Oxygen Club of California. 2006. Oxidants and antioxidants in biology. Book of abstracts. 15-18 march 2006. Santa barbara California. 87.
- Rydlovskaya A.V., Makarov V.G., Makarova M.N., Tikchonov V.P. Investigation of anti- inflammatory activity of complex herbal oil extract in vitro and in vivo // Oxygen Club of California. 2006. Oxidants and antioxidants in biology. Book of abstracts. 15-18 march 2006. Santa barbara California. 107
- Макаров В.Г., Макарова М.Н., Селезнева А.И. Сравнительная оценка антирадикальной активности флавоноидов // Человек и его здоровье. -2005. сборник посвящен 60- летию Победы в Великой Отечественной войне: / Под редакцией акад. РАМН А.В. Шаброва, проф. В.Г. Маймулова/ -СПб: ГМА им. И.И. Мечникова. -2005. С.166
- Макарова М.Н., Александрова А.Е., Макаров В.Г., Селезнева А.И. Тесакова С.В. Оценка антиоксидантных и антигипоксических свойств экстрактов бадана // Гипоксия: механизмы, адаптация коррекция. Материалы Четвертой Российской конференции 12-14 октября 2005., Москва. С.73.
- Makarova M.N., Selezneva A.I. Activity of flavonoids in lipid peroxidation reactions // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2005, 22-25 июня: Матер. IX международного съезда. – Санкт-Петербург, Россия. – 2005. С. 808.
- Макарова М.Н., Макаров В.Г. Обзор методов оценки антирадикальной активности природных соединений // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2005, 22-25 июня: Матер. IX международного съезда. – Санкт-Петербург, Россия. – 2005. С.102-116
- Макарова М.Н., Макаров В.Г., Александрова А.Е., Селезнева А.И. Тесакова С.В. Изучение антиоксидантной и антигипоксической активности экстрактов бадана тостолистного // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2005, 22-25 июня: Матер. IX международного съезда. – Санкт-Петербург, Россия. – 2005. С.94-102.
- Макаров В.Г., Макарова М.Н., Селезнева А.И. Изучение механизма антиоксидантного действия витаминов и флавоноидов // Вопросы питания. -2005. –Т. 74, №1. –С. 10-13
- Макарова М.Н., Макаров В.Г., Станкевич Н.М., Ермаков С.Б., Яшакина И.А. Характеристика антирадикальной активности экстрактов из растительного сырья и содержание в них дубильных веществ и флавоноидов. // Растительные ресурсы. -2005, вып. 2. –С. 106-115.
- Макаров В.Г., Макарова М.Н., Селезнева А.И. Антирадикальная активность витаминов по отношению к гидроксильному радикалу и супероксидному радикалу // Клиническая фармакология в России: достижения и перспективы. 9-10 сентября 2004. Матер. Научно-практич. конференции с международным участием. – Москва. – 2004. С.138-140.
- Александрова А.Е., Макарова М.Н. Антигипоксическая и антиоксидантная активность синтетических и природных препаратов // Клиническая фармакология в России: достижения и перспективы. 9-10 сентября 2004. Матер. Научно-практич. конференции с международным участием. – Москва. – 2004. С. 5-9.
- Макарова М.Н., Макаров В.Г., Станкевич Н.М., Ермаков С.Б., Яшакина И.А. Характеристика антирадикальной активности и состава экстрактов из растительного сырья //Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2004, 21-23 июня: Матер. VIII международного съезда. – Миккели, Финляндия. – 2004. С. 464-470.
- Александрова А.Е., Макаров В.Г., Рыженков В.Е., Макарова М.Н., Шиков А.Н. Противовоспалительная активность и механизм действия нового комплексного растительного средства //Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2004, 21-23 июня: Матер. VIII международного съезда. – Миккели, Финляндия. – 2004. С.345-352.
- Макаров В.Г., Макарова М.Н. Антиоксиданты и реакционно-активные формы кислорода. Их роль и механизм действия // Актуальные проблемы создания новых лекарственных препаратов природного происхождения – Фитофарм. – 2004, 21-23 июня: Матер. VIII международного съезда. – Миккели, Финляндия. – 2004. С.121-132.
- Макарова М.Н., Селезнева А.И., Макаров В.Г., Зенкевич И.Г. Изучение антирадикальной активности витаминов // Новые технологии в медицине: Сб. докл. Первой международной дистационной науч.- практ. конференции, 15 – 30 марта 2004 года. – СПб., 2004 г. С. 101.
- Makarov V.G., Makarova M.N., Zenkevich I.G. Scavenging activity of polyphenolic compounds to hydroxyl radical // International Workshop «Progress in Biotechnology and Neurobiology – Integrative Medicine» Hurgada, Egipt, Africa, 14- 24 February 2004 P. 20-21.
- Макарова М.Н., Селезнева А.И., Макаров В.Г., Зенкевич И.Г. Изучение антирадикальной активности витаминов по отношению к гидроксильному радикалу // Материалы 2-ой межрегиональной научно- практической конференции: Питание здорового и больного человека, Санкт – Петербург. – 2004 г. С. 141-142.
- Макарова М.Н., Селезнева А.И., Макаров В.Г., Зенкевич И.Г. Оценка антирадикальной активности водо- и жирорастворимых витаминов по отношению к гидроксильному радикалу // Проблемы укрепления здоровья и профилактика заболеваний/ Под ред. акад. РАМН А.В. Шаброва, проф. В.Г. Маймулова. – СПб.:СПбГМА им. И.И. Мечникова – 2004 г. С.172-173.
- Макарова М.Н., Макаров В.Г., Зенкевич И.Г. Антирадикальная активность флавоноидов и их комбинации с другими антиоксидантами // Фармация. -2004, № 2. –С. 30-32.
- Makarov V.G., Makarova M.N., Alexandrova A.E., Ryzhenkov V.E The role of antioxidant system in gastroprotective action of camomille (Matricaria vrecutita L.) oil extract in stress – induced stomach mucous ulceration // Психофармакология и биологическая наркология. – 2004. № 2-3 С. 706 – 707.
- Макаров В.Г., Макарова М.Н., Селезнева А.И. Сравнительная оценка антирадикальной активности флавоноидов по отношению к гидроксильным и супероксиданион радикалам в экспериментах in vitro // Вестн. СПбГМА им. И.И. Мечникова. -2004. – № 4. -С. 108-110.
- Makarova M.N., Kuznetsov A.S., Dadali V.A., Makarov V.G., Zenkevich I.G. The fluorimetric method for of hydroxyl radical scavenging activities of natural antioxidant // GA. Book of abstracts. Fascination facts future. August 31 – September 4. – 2003/ – Kiel, Germany. 101.
- Александрова А.Е., Макарова М.Н., Макаров В.Г., Куренкова Т.Ю. Действие Гастроромазола на перекисное окисление липидов и антиоксидантный статус в условиях экспериментального язвообразования // Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. VI международного съезда. –СПб. –2002. –С. 344-349.
- Макарова М.Н. Изучение антиоксидантной активности фитопрепаратов в условиях токсического гепатита // Проблемы охраны здоровья населения и окружающей среды: Тезисы науч. конференции. -СПб. -2002. -С. 178-179.
- Макарова М.Н., Александрова А.Е., Макаров В.Г., Куренкова Т.Ю. Изучение антиоксидантной активности препаратов на основе семян сосны кедровой сибирской (Semina pini sibiricae du tour) // Биохимия – медицине: Матер. международной науч. конференции. -Махачкала. -2002. -С. 223-226.
- Макарова М.Н., Александрова А.Е., Дадали В.А., Макаров В.Г. Влияние масла ромашки на состояние антиоксидантной системы при экспериментальном язвенном поражении слизистой желудка // III Съезд биохимического общества: Тезисы науч. докладов. -СПб. -2002. -С. 189-190.
- Макарова М.Н., Дадали В.А., Макаров В.Г., Зенкевич И.Г. Характеристика антирадикальной активности некоторых природных биологически активных соединений //Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. VI международного съезда. –СПб. –2002. –С. 441-444.
- Макарова М.Н., Кузнецов А.С., Дадали В.А. Оценка антирадикальной активности флавоноидов in vitro // Биохимия – медицине: Тезисы Всеросийской науч. конференции, посвящ 110-летию каф. клин. биохимии и лаб. диаг. ВМА и 100-летию со дня рожд. акад. АМН СССР Г.Е. Владимирова. -СПб. -2002. -С. 53.
- Макарова М.Н., Кузнецов А.С., Дадали В.А., Макаров В.Г., Зенкевич И.Г. Новый биохимический метод коррекции болезненных и патологических состояний человека на основе механизмов свободно-радикального окисления // Вестн. БПА. Матер. науч. сессии, посвящ. памяти проф. А.С. Мозжухина. -СПб. -2002. -Вып. 45. -С. 100-107.
- Макарова М.Н., Кузнецов А.С., Зенкевич И.Г., Макаров В.Г. Флуориметрический метод оценки антирадикальной активности природных антиоксидантов по отношению к гидроксильным радикалам // Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. VI международного съезда. –СПб. –2002. –С. 437-441.
- Макарова М.Н., Куренкова Т.Ю., Белозерова А.К., Закревский В.В., Макаров В.Г. Применение показателя антирадикальной емкости плазмы крови у больных с аднекситом // Вестн. СПбГМА им. И.И. Мечникова. -2002. -№ 1-2 (3) -С. 110-112.
- Makarova M.N., Kuznetsov A.S., Dadali V.A., Makarov V.G., Zenkevich I.G. Study of hydroxyl radical scavenging activity of polyphenolic compounds // Reactive Oxygen and Nitrogen Species: diagnostic, preventive and therapeutic values: Poster International symposium. -St.-Petersburg-Kizhi- St.-Petersburg. -2002. -C. 128.

















































