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
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
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
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 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
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
Hepatoprotective effects of granulocytic CSF were studied using experimental model of CCl4-induced hepatitis. It was found that treatment with granulocytic CSF increased the content of stromal precursors and mesenchymal stem cells in the bone marrow and peripheral blood with subsequent increase in the number of hepatic precursor cells in the liver. These findings attest to mobilization of progenitor mesenchymal cells and their migration into damages liver tissue, which accelerates its regeneration related to changes in the parenchyma, but not connective tissue development.
