ABSTRACT
We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.
Subject(s)
Radiopharmaceuticals/adverse effects , Aluminum Oxide/adverse effects , Animals , Body Temperature/drug effects , Female , Heart/drug effects , Kidney/drug effects , Liver/drug effects , Male , Mice , Nanoparticles/adverse effects , Nervous System/drug effects , Rabbits , Rats , Technetium/adverse effectsABSTRACT
Intramuscular injections of Relatox in therapeutic and toxic doses to young outbred laboratory rats for 14 days caused no changes in the peripheral blood and bone marrow parameters, serum biochemical parameters, and morphology of the major viscera. In the toxic dose, the drug caused local irritation (inflammation, atrophy, and sclerosis in muscle tissue). Regeneration processes started in muscle tissue 7 days after Relatox withdrawal.
Subject(s)
Botulinum Toxins, Type A/toxicity , Exploratory Behavior/drug effects , Hemagglutinins/toxicity , Locomotion/drug effects , Paresis/chemically induced , Animals , Animals, Outbred Strains , Atrophy , Botulinum Toxins, Type A/pharmacology , Drug Combinations , Edema/chemically induced , Edema/pathology , Female , Hemagglutinins/pharmacology , Hindlimb , Injections, Intramuscular , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscle, Skeletal/physiology , Myofibrils/drug effects , Myofibrils/pathology , Organ Size/drug effects , Paresis/pathology , Rats , Regeneration , Sexual Maturation , Viscera/drug effects , Weight Loss/drug effectsABSTRACT
High hepatoprotective activity of granulocytic CSF and hyaluronidase immobilized using electron-beam immobilization technology was demonstrated on the model of CCl(4)-induced hepatitis: the preparations produced anticholestatic, anti-inflammatory, and antisclerotic effects. These effects developed against the background of stimulation of bone marrow multipotent precursor cells and their mobilization into circulation accompanied by an increase in the content of parenchymatous progenitor cells in the liver. The most pronounced positive effect was observed in combined treatment with the test preparations.
Subject(s)
Enzymes, Immobilized/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hepatitis, Chronic/drug therapy , Hyaluronoglucosaminidase/therapeutic use , Animals , Male , Mice , Nanotechnology , Rats , Rats, Wistar , Regenerative MedicineABSTRACT
Pharmacological characteristics of somatotropin pegylated using electron-beam synthesis nanotechnology (PEG-STH) were studied. Oral PEG-STH stimulated the intensity of protein and lipid metabolism and endochondral bone growth without modifying the processes of periosteal and endosteal bone formation. Specific activity of this substance administered orally significantly surpassed that of parenteral non-modified growth hormone.
Subject(s)
Bone Development/drug effects , Human Growth Hormone/pharmacology , Lipid Metabolism/drug effects , Nanotechnology , Polyethylene Glycols , Proteins/metabolism , Animals , Male , Rats , Rats, WistarABSTRACT
Administration of enzyme preparation Trombovazim as a corrector of ischemic damage to animals with experimental liver ischemia-reperfusion reduces neutrophilic infiltration of liver parenchyma and decreases hyperfermentemia, which attests to a decrease in the intensity of destructive changes in hepatocytes.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Liver Diseases/drug therapy , Reperfusion Injury/drug therapy , Animals , Liver Diseases/immunology , Male , Neutrophil Infiltration/drug effects , Rats , Reperfusion Injury/immunologyABSTRACT
The effect of immobilized granulocyte CSF on morphological characteristics and functional state of the liver was studied during chronic toxic hepatitis. The mechanisms of the therapeutic action of this agent were evaluated. The product had a strong hepatoprotective effect and exhibited the antiinflammatory and antisclerotic properties. The mechanism of activation of reserve systems for cell renewal (involved in restoration of the liver tissue) is probably related to an increase in proliferative activity of early precursor cells in the bone marrow, mobilization of these cells into the peripheral circulation, and directed homing into the liver tissue where they activate local regenerative mechanisms and prevent hepatocyte destruction. It should be emphasized that the concentration of SDF-1 increases in the liver tissue, but decreases in the bone marrow. These changes create the concentration gradient, which determines the migration of undifferentiated precursor cells to the liver.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Chemokine CXCL12/metabolism , Granulocyte Colony-Stimulating Factor/pharmacology , Hepatitis, Chronic/metabolism , Liver/physiopathology , Animals , Bone Marrow/metabolism , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Hepatocytes/metabolism , Liver/drug effects , Liver/pathology , Male , Mice , Mice, Inbred CBA , Rats , Rats, WistarABSTRACT
The influence of various antineoplastic preparations (farmorubicin, paclitaxel, etoposide, platidiam) on morphological and functional status of the liver in experimental animals was studied. It is shown, that all these antineoplastic drugs possess strong hepatotoxic activity and thereby cause toxic hepatitis and increase activity of hepatic enzymes. Biochemical parameters were normalized within 30 days after treatment whereas morphological changes persisted somewhat longer.
Subject(s)
Antineoplastic Agents/toxicity , Chemical and Drug Induced Liver Injury/pathology , Liver/drug effects , Animals , Chemical and Drug Induced Liver Injury/metabolism , Disease Models, Animal , Follow-Up Studies , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Male , Rats , Risk FactorsABSTRACT
Antiinflammatory effects of water-alcohol extracts and sum of alkaloids from the aerial part of delphinium under conditions of immune inflammation caused by Freund's complete adjuvant were comparable to activity of orthophen, a classical antiinflammatory drug. Normalizing effects of the studied extracts on hematological and biochemical parameters were demonstrated.
Subject(s)
Alkaloids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Delphinium/chemistry , Freund's Adjuvant/pharmacology , Plant Extracts/therapeutic use , Alkaloids/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Arthritis, Experimental/chemically induced , Arthritis, Experimental/pathology , Edema/chemically induced , Edema/drug therapy , Extremities , Hyperemia/chemically induced , Hyperemia/drug therapy , Male , Plant Extracts/chemistry , RatsABSTRACT
Preclinical study of the safety of 6 preparations containing ultralow doses of antibodies to endogenous regulators showed that they are relatively safe, are well tolerated by animals in doses more than 1000-fold surpassing the therapeutic dose for humans, and produce no general toxic effect on the organism of laboratory animals.
Subject(s)
Antibodies/toxicity , Toxicity Tests , Animals , Antibodies/administration & dosage , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/toxicity , Dose-Response Relationship, Drug , Mice , Rabbits , RatsABSTRACT
Using the model of alloxan-induced diabetes mellitus on rats we demonstrated the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of the pancreas and normalization of blood glucose concentration. The preparation produced an antiinflammatory and antisclerotic effects associated with activation of stem cells and their determined homing into the pancreas.
Subject(s)
Antibodies/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Granulocyte Colony-Stimulating Factor/immunology , Pancreas/drug effects , Animals , Antibodies/immunology , Diabetes Mellitus, Experimental/pathology , Female , Male , Mice , Mice, Inbred CBA , Pancreas/pathologyABSTRACT
Single intravenous injection of paclitaxel to rats in a maximum tolerated dose of 4.6 mg/kg was accompanied by permanent structural and functional changes in the liver. The observed changes were typical of nonspecific reactive hepatitis: infiltration with lymphocytes and macrophages, pyknosis, and focal fatty degeneration of hepatocytes. Liver enzyme activity increased in blood plasma.
Subject(s)
Antineoplastic Agents, Phytogenic/toxicity , Hepatocytes , Liver/drug effects , Liver/pathology , Paclitaxel/toxicity , Animals , Biomarkers/blood , Female , Hepatocytes/cytology , Hepatocytes/drug effects , Liver/enzymology , RatsABSTRACT
We have carried out a preclinical toxicological investigation (acute toxicity evaluation) of Mangascan (0.5 M solution of manganese(II) - EDTA complex) and Pentamang (0.5 M solution of manganese(II) - DTPA complex), a new paramagnetic contrast agents for MRI procedures. In 14 days after single intravenous introduction of Mangascan (10.0 ml/kg) or Pentamang (5.0 ml/kg) to rats, no any toxic influence of the studied agents was detected in the general condition, bone marrow, cardiovascular and central nervous systems, and liver and kidney functions of experimental animals. No pathological changes were observed in the functional activity and morphology of the internal organs and systems. The results showed that both Mangascan and Pentamang belong to the class of low toxicity substances.
Subject(s)
Contrast Media/toxicity , Edetic Acid/toxicity , Pentetic Acid/toxicity , Animals , Female , Magnetic Resonance Imaging , Male , Mice , RatsABSTRACT
We studied the mechanisms of therapeutic effects of granulocytic colony-stimulating factor in experimental diabetes mellitus. It was found that this preparation increased the number of mesenchymal precursor cells in the bone marrow and peripheral blood with subsequent increase in the content of progenitor cells in the pancreas. These results attest to mobilization of mesenchymal progenitor cells and their migration into the damaged tissue accompanied by morphofunctional recovery of the insulin-producing apparatus.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Animals , Cell Movement/drug effects , Cell Movement/physiology , Diabetes Mellitus, Experimental/chemically induced , Female , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , MiceABSTRACT
We studied the state of the pools of mesenchymal precursor cells in the bone marrow and peripheral blood and the dynamics of regional precursor cells in the liver in experimental chronic hepatitis. We showed that bone marrow mesenchymal stem cells are involved in liver regeneration in its chronic disease. Our results suggest that these mechanisms are insufficient for the recovery of liver tissue.
Subject(s)
Bone Marrow Cells/pathology , Chemical and Drug Induced Liver Injury/pathology , Hepatitis, Chronic/pathology , Mesenchymal Stem Cells/pathology , Animals , Carbon Tetrachloride Poisoning/pathology , Female , Liver/pathology , Male , Mice , RatsABSTRACT
The safety of the new enterosorbent noolit has been evaluated within the framework of its preclinical characterization. Single introduction of noolit to rats and mice (females and males) in maximum doses for intragastric administration (5.0 - 20.0 g/kg) does not lead to the loss of experimental animals. Single administration of large doses (5 - 40 times the effective dose) can reduce the growth of the total body weight and lead to the development of nonlethal pathological changes of hemopoietic organs, which is manifested by a weak regenerative anemia (5% of cases); neutrophile, eosinophile, and basophile leukocytosis (3% of cases); and a decrease in the glucose level in blood serum. In chronic experiments on rabbits, the administration of noolit for 3 months in a dose of 0.5 and 2.0 g/kg (2 and 8 times that recommended for humans) did not reveal any toxic action on the functional and morphological state of the main systems and organs (blood, liver, kidneys, lungs, heart, gastrointestinal tract, sex organs, etc.).
Subject(s)
Aluminum Oxide/pharmacology , Enterosorption , Lithium Compounds/pharmacology , Organosilicon Compounds/pharmacology , Aluminum Oxide/toxicity , Anemia/chemically induced , Animals , Blood Cells/drug effects , Blood Glucose/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Hematopoiesis/drug effects , Humans , Lithium Compounds/toxicity , Male , Mice , Organosilicon Compounds/toxicity , Rabbits , Rats , Time FactorsABSTRACT
Experiments show that ethanol extracts prepared from the above-ground parts of Aconitum baicalensis and the above-ground parts and roots of Aconitum septentrionale L. suppressed the exudative and proliferative stages of model chronic inflammation. Both phytopreparations normalized some biochemical indices of the blood (total protein, seromucoids, firbinogen) altered by the inflammation.
Subject(s)
Aconitum/chemistry , Granuloma/prevention & control , Plant Components, Aerial/chemistry , Plant Extracts/administration & dosage , Plant Roots/chemistry , Animals , Ethanol/chemistry , Male , RatsABSTRACT
We studied the state of pools of mesenchymal precursor cells of different maturity in the bone marrow and peripheral blood and the dynamics of the content of regional parenchymal stem cells and stromal precursors in the pancreas during experimental diabetes mellitus. Reduced content of organ-specific stem cells and increased content of stromal precursors in the pancreas in the absence of compensatory reaction of deep reserve mechanisms, mesenchymal bone marrow cells, were revealed.
Subject(s)
Bone Marrow Cells/cytology , Diabetes Mellitus, Experimental/pathology , Mesenchymal Stem Cells/cytology , Pancreas/cytology , Animals , Female , Histological Techniques , Image Processing, Computer-Assisted , Male , Mice , Mice, Inbred CBA , Statistics, Nonparametric , Time FactorsABSTRACT
The hepatoprotective effects of superlow dose preparation of antibodies to granulocytic CSF were studied on a model of CCl4-induced hepatitis. The preparation exhibited high antiinflammatory and antisclerotic activities determined by stimulation, mobilization, and determined homing of mesenchymal stem cells into damaged liver with subsequent differentiation of these cells into mature hepatocytes.
Subject(s)
Antibodies/chemistry , Granulocyte Colony-Stimulating Factor/immunology , Liver/chemistry , Animals , Cell Differentiation , Female , Granulocyte Colony-Stimulating Factor/metabolism , Hepatitis/metabolism , Hepatocytes/metabolism , Liver/metabolism , Male , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred CBA , Rats , Receptors, Granulocyte Colony-Stimulating Factor/metabolism , Stem Cells/metabolismABSTRACT
The effects of administration of the parent substance of high-molecular-weight poly(ethylene oxide) (HMWPEO) with a molecular mass of 3-6 x 10(6) D and the related drug polyetox (representing a water-soluble lyophilized form of HMWPEO suitable for intravenous injection) on the characteristics of peripheral blood and bone marrow were studied in rats. HMWPEO was injected intravenously and intraperitoneally in a single toxic dose. Polyetox was injected intraperitoneally in a therapeutic dose and in 3- and 10-fold doses over a period of 30 days. Single i.v. and i.p. injections of HMWPEO in the maximum tolerable dose leads to a dose-dependent reversible hemolytic anemia of medium degree, neutrophilic leukocytosis, lymphopenia, and thrombocytopenia. The chronic i.p. adminstration of polyetox in a 10-fold therapeutic dose caused red blood cell lysis and led to the development of reversible regenerative anemia.
Subject(s)
Anemia, Hemolytic/chemically induced , Bone Marrow/drug effects , Hematologic Diseases/chemically induced , Polyethylene Glycols/toxicity , Animals , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Injections, Intravenous , Male , RatsABSTRACT
The antistressor and antioxidant properties of preparations from the underground part of elfwort (Inula helenium) were studied on a model of acute stress in mice. The preparations produced a protective effect with respect to internal organs, blood, carbohydrate metabolism, and lipid peroxidation process.
