ABSTRACT
A new D-glucuronic acid (DGA) preparation was studied for toxicological safety on a preclinical level. The results obtained upon a single acute DGA administration in rats, mice, and rabbis showed that the drug exhibits moderate toxicity. A one-month treatment of rats (at a single daily dose of 50, 250, and 500 mg/kg, i.p.) and dogs (50 mg/kg, i.v.) induced neither functional nor morphological changes in hemopoietic and lymphoid organs, kidney, heart, as well as in the digestive, nervous, hemostatic, and fibrinolytic systems. The intraperitoneal administration of DGA produced a pronounced local irritation effects. The liver of both rats and dogs treated with DGA showed dose-dependent adipose degeneration, which decreased upon the drug abolition. The administration of DGA in 50, 100, and 250 mg/kg doses led to dose-dependent changes in some characteristics of the reproductive system in rats. DGA did not modify the extent of allergic reactions and showed no immunotoxicant and mutagen properties.
Subject(s)
Glucuronic Acid/toxicity , Animals , Antibody Formation , Dogs , Dose-Response Relationship, Drug , Female , Glucuronic Acid/administration & dosage , Glucuronic Acid/chemistry , Guinea Pigs , Hypersensitivity/etiology , Immunity, Cellular/drug effects , Lethal Dose 50 , Male , Mice , Mice, Inbred BALB C , Mutagenicity Tests , Rats , Reproduction/drug effects , Toxicity Tests, AcuteABSTRACT
The effect of 10(3)-10(5) E/20 g doses of the recombinant factor of human beta tumor necrosis (rFNT-beta) on formation of the immune response and macrophage functional activity was studied in CBA and C57Bl/6 mice that differ in genetically determined level of the immune response to an antigen (sheep erythrocytes). The rFNT-beta was found to cause a modulating effect on the cell and humoral links of the immune response. The effect of the agent depended on the dose and the genotype of the experimental animals. It is suggested that the interlinear differences in the intensity of the humoral immune response in rFNT-beta administration may be connected with the different sensitivity to the agent of the peritoneal macrophages of mice of the used lines.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antigen-Antibody Reactions/drug effects , Lymphotoxin-alpha/pharmacology , Animals , Antibody Formation/drug effects , Antibody-Producing Cells/drug effects , Antibody-Producing Cells/immunology , Antigen-Antibody Reactions/immunology , Dose-Response Relationship, Drug , Humans , Immunity, Cellular/drug effects , Immunization/methods , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Phagocytosis/drug effects , Recombinant Proteins/pharmacology , Species SpecificityABSTRACT
Experiments on CBA/Ca Lac mice showed that pantohematogen, a drug prepared from whole blood of Siberian deer, wapiti, and deer, when administered in a course in doses under study and in chosen conditions of the experiment does not possess allergenic and immunotoxic properties. The immunomodulating properties of the drug were characterized by marked stimulation of macrophage phagocytic activity and, under definite conditions, by activation of formation of antibody-producing cells in the spleen of mice immunized with sheep erythrocytes.
Subject(s)
Adjuvants, Immunologic/pharmacology , Allergens/pharmacology , Animals , Antibody-Producing Cells/drug effects , Antibody-Producing Cells/immunology , Deer/blood , Dose-Response Relationship, Drug , Immunization/methods , Mice , Mice, Inbred CBA , Phagocytosis/drug effects , Phagocytosis/immunology , Spleen/drug effects , Spleen/immunology , Time FactorsABSTRACT
A relationship between cellular immunity and general adaptation syndrome in the course of CAM polychemotherapy has been investigated. The results point to a lack of lymphopenia, lower levels of T-suppressors and higher instability of immunological indices in patients showing increased activation reaction and maximum antitumor resistance during cytostatic therapy, unlike in those in stress. This opens an opportunity for correction.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lymphocytes/drug effects , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/immunology , Doxorubicin/immunology , Female , Humans , Male , Methotrexate/immunology , Middle Aged , T-Lymphocytes/drug effectsABSTRACT
The cytogenetic effects of antitumor drugs with different action mechanism on the genetic structure of bone marrow hemopoietic cells were studied in experiments on CBA mice. It has been shown that single injections of doxorubicin (6 mg/kg), vinblastin (2.2 mg/kg), cyclophosphamide (250 mg/kg) and continuous administration of doxorubicin (0.95 mg/kg), vinblastin (0.24 mg/kg), cyclophosphamide (27 mg/kg) in 1/10 LD50 x 10 induce the formation of bone marrow cells with cytogenetic damage and peripheral red blood cells with micronuclei. The cytogenetic damage of hemopoietic tissue may be detectable 1-3 months after cytostatic influence.
