RESUMEN
Morphological and functional characteristics of spermatogenesis in rats were studied during the early and delayed periods after single injection of paclitaxel (antitumor agent) in the maximum tolerated dose. The drug induced structural changes in the gonads associated with oligospermia and increased number of pathological forms of spermatozoa with reduced functional activity.
Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacología , Paclitaxel/farmacología , Espermatogénesis/efectos de los fármacos , Animales , Masculino , Oligospermia/inducido químicamente , Ratas , Espermatozoides/efectos de los fármacos , Espermatozoides/fisiologíaRESUMEN
Combined stimulatory effect of antiserotonin drug and erythropoietin on the bone marrow erythropoiesis was studied under conditions of cytostatic myelosuppression. The stimulatory effect of erythropoietin on regeneration of the hemopoietic erythroid stem increased, if serotonin mediation in the CNS was disordered before induction of cytostatic myelosuppression. The stimulatory effect of a combination of cyproheptadine and epocrine (experimental group) significantly surpassed that of cyproheptadine and epocrine monotherapies. The increase in the content of erythroid elements in the blood system of experimental animals was due to recovery of the structural and functional integrity of the hemopoietic tissue (at the expense of reduction of the suppressive effect of CNS serotonin on the formation of erythroid hemopoietic islets) and simultaneous stimulation of division and maturation of erythroid precursors with epocrine.
Asunto(s)
Médula Ósea/efectos de los fármacos , Ciproheptadina/farmacología , Eritropoyesis/efectos de los fármacos , Eritropoyetina/farmacología , Fluorouracilo/toxicidad , Inmunosupresores/toxicidad , Antagonistas de la Serotonina/farmacología , Animales , Femenino , Ratones , Ratones Endogámicos CBARESUMEN
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.
Asunto(s)
Anticuerpos/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/inmunología , Páncreas/efectos de los fármacos , Animales , Anticuerpos/inmunología , Diabetes Mellitus Experimental/patología , Femenino , Masculino , Ratones , Ratones Endogámicos CBA , Páncreas/patologíaRESUMEN
On the model of skin flap we studied the possibility of stimulating the processes of wound healing with a preparation containing ultralow doses of antibodies to granulocytic colony-stimulating factor. The preparation accelerated tissue regeneration against the background of mobilization of bone marrow mesenchymal precursor cells into circulation accompanied by an increase in the number of stromal precursor cells in the area of lesion.
Asunto(s)
Anticuerpos/inmunología , Anticuerpos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/inmunología , Células Madre Mesenquimatosas/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Femenino , Masculino , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Endogámicos CBARESUMEN
We studied the possibility of modification of hematotropic effects of granulocytic CSF and hyaluronidase. It was found that hyaluronidase in a dose of 20 U/mouse potentiates the specific effect of granulocytic CSF on granulocytopoiesis, while granulocytic CSF potentiates the stimulating effect of the enzyme on the erythroid stem. Functional activity of hemopoiesis precursors, secretion of humoral factors by adherent myelokaryocytes, and serum content of hemopoietins increased under these conditions. Hyaluronidase (100 U/mouse) against the background of treatment with granulocytic CSF leads to uncoupling of proliferation and differentiation of hemopoietic cells and abolishes the mutually activating hematotropic effect of preparations.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Granulocitos/efectos de los fármacos , Hematopoyesis/efectos de los fármacos , Hialuronoglucosaminidasa/farmacología , Animales , Femenino , Granulocitos/citología , Masculino , RatonesRESUMEN
We studied the role of central adrenergic structures in the regulation of granulocytic hemopoietic stem during cytostatic treatment. It was found that brain norepinephrine promoted the decrease in functional activity of adherent mononuclears of the hemopoiesis-inducing environment, cytokine-dependent and alpha-adrenergic mechanisms of regulation of division and maturation of granulomonocytic precursors under conditions of cyclophosphamide treatment. Under conditions of 5-fluorouracil treatment, the effect of the adrenergic system was aimed at the formation of granulocytic and fibroblast-type cell complexes, activation of the production of colony-forming activity by microenvironmental cells, and acceleration of maturation of neutrophilic granulocytes associated with the system of granulocytic CSF and peripheral alpha-adrenergic structures.
Asunto(s)
Sistema Nervioso Central/fisiología , Citostáticos/farmacología , Granulocitos/fisiología , Hematopoyesis/efectos de los fármacos , Receptores Adrenérgicos/metabolismo , Inhibidores de Captación Adrenérgica/farmacología , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Diferenciación Celular/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Evaluación Preclínica de Medicamentos , Femenino , Fluorouracilo/farmacología , Granulocitos/efectos de los fármacos , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/efectos de los fármacos , Ratones , Ratones Endogámicos CBA , Reserpina/farmacología , Factores de TiempoRESUMEN
Immune reactions of the progeny of female Wistar rats injected with paclitaxel a single MPD of 1 and 3 months before mating with intact males were studied. Thymic hyperplasia was detected in the progeny of female rats mated 1 month after treatment. Disorders in the antibody-specific and antibody-nonspecific mechanisms of the immune response were detected in the progeny of females mated with intact males 3 months after cytostatic treatment.
Asunto(s)
Inmunidad/efectos de los fármacos , Paclitaxel/toxicidad , Animales , Animales Recién Nacidos , Citostáticos/toxicidad , Femenino , Hiperplasia/inducido químicamente , Inmunidad/inmunología , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Wistar , Timo/efectos de los fármacos , Timo/patología , Factores de TiempoRESUMEN
We studied the state of the bone marrow Thy-1,2+ cell pool under conditions of severe hypoxia. T cell mechanisms of hemopoiesis regulation are preserved under conditions of severe oxygen deficiency due to changes in functional properties of Thy-1,2+ cells. We revealed an indirect (mediated through cooperation with adherent myelokaryocytes) stimulating effect of Thy-1,2+ cells on erythroid precursors as well as direct and indirect feeder effects of these cells on granulocyte-monocyte precursors.
Asunto(s)
Células de la Médula Ósea/patología , Hematopoyesis , Hipoxia/sangre , Antígenos Thy-1/metabolismo , Anemia Hemolítica/sangre , Anemia Hemolítica/etiología , Animales , Reacción de Prevención , Volumen Sanguíneo , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Adhesión Celular , Células Precursoras Eritroides/patología , Células Precursoras Eritroides/fisiología , Células Precursoras de Granulocitos/patología , Células Precursoras de Granulocitos/fisiología , Hidroxibutiratos/farmacología , Hipoxia/complicaciones , Hipoxia/fisiopatología , Memoria , Ratones , Ratones Endogámicos CBA , Linfocitos T/fisiologíaRESUMEN
Binding of mesenchymal precursor cells to intact extracellular matrix and stroma increased under the effect of hyaluronidase and decreased after treatment of adhesion substrates with the enzyme. The stimulation of the release of progenitor elements into the blood by granulocytic CSF depended on the interaction of mesenchymal precursors with the feeder stimulating bone marrow microenvironment. Additional in vivo treatment with hyaluronidase potentiated mobilization of precursor cells by granulocytic CSF against the background of increased affinity of precursor to the stroma.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética , Hialuronoglucosaminidasa/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos CBARESUMEN
We studied the role of cell components and extracellular matrix of the microenvironment in the mechanisms of mobilization of mesenchymal bone marrow stem cells under the effect of granulocyte colony-stimulating factor in vitro and in vivo on CBA/CaLac mice. It was found that the mechanisms underlying the dissociation effect of granulocyte colony-stimulating factor do not include its direct effect on the interaction of precursor cells with fibronectin. The major role in this process is played by changes in functional state of stromal precursors and cell component of the microenvironment induced by granulocytic colony-stimulating factor and mediated by regulatory systems of the microorganism.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/fisiología , Células Madre Mesenquimatosas/fisiología , Animales , Femenino , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Ratones Endogámicos CBARESUMEN
The effects of dimethylsulfoxide on the state of mesenchymal precursors in vivo were demonstrated. Treatment with dimethylsulfoxide reduced the content of stromal clonogenic elements in the bone marrow and inhibited mobilization of mesenchymal precursors induced by granulocyte colony-stimulating factor. In in vitro system, dimethylsulfoxide inhibited proliferation of fibroblast, erythroid, and granulomonocytic colony-forming units and stimulates maturation of hemopoietic precursors.
Asunto(s)
Dimetilsulfóxido/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Ensayo de Unidades Formadoras de Colonias , Dimetilsulfóxido/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Hematopoyesis/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , RatonesRESUMEN
The possibility of using hyaluronidase for the regulation of the state of different pools of mesenchymal precursors in vivo was demonstrated. The reaction of mesenchymal precursor cells depended on the dose of the enzyme. Administration of hyaluronidase in a dose of 20 U/mouse increased the content of stromal precursors and mesenchymal stem cells in the bone marrow and promotes mobilization of precursor cells induced by granulocyte CSF. Administration of high dose of hyaluronidase (100 U/mouse) reduced the content of mesenchymal precursors in hemopoietic tissue and abolished granulocyte CSF-induced mobilization of mesenchymal precursor cells of different maturity.
Asunto(s)
Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ensayo de Unidades Formadoras de Colonias , Relación Dosis-Respuesta a Droga , Femenino , Factor Estimulante de Colonias de Granulocitos/farmacología , Hialuronoglucosaminidasa/administración & dosificación , Hialuronoglucosaminidasa/farmacología , Masculino , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos CBARESUMEN
The role of the dopaminergic system in the regulation of the granulocytic hemopoietic stem was studied after administration of cyclophosphamide and 5-fluorouracil. Dopamine in the central nervous system promotes the development of cytostatic-induced myelosuppressions. The inhibitory effect of dopaminergic structures on granulocytopoiesis after administration the fluoropyrimidine antimetabolite was of shorter duration compared to that observed in experiments with the alkylating agent. The inhibitory effect of brain dopamine is associated with a decrease in proliferative activity and differentiation of granulomonocytic precursors, prevention of hemopoietic islet formation, and impairment of secretion of colony-stimulating activity in adherent cells of the hemopoiesis-inducing microenvironment. Cyclophosphamide and 5-fluorouracil had different effects on the rate of hemopoietic tissue regeneration, which was related to specific interaction between distant regulatory structures and hemopoiesis-inducing microenvironment and differences in the influence of cytostatics on hemopoietic and stromal cells.
Asunto(s)
Citostáticos/farmacología , Dopamina/metabolismo , Granulocitos , Hematopoyesis/fisiología , Agonistas Mieloablativos/farmacología , Animales , Encéfalo/metabolismo , Ciclofosfamida/farmacología , Antagonistas de Dopamina/farmacología , Femenino , Fluorouracilo/farmacología , Granulocitos/efectos de los fármacos , Granulocitos/fisiología , Haloperidol/farmacología , Células Madre Hematopoyéticas/metabolismo , Ratones , Ratones Endogámicos CBARESUMEN
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.
Asunto(s)
Células de la Médula Ósea/citología , Diabetes Mellitus Experimental/patología , Células Madre Mesenquimatosas/citología , Páncreas/citología , Animales , Femenino , Técnicas Histológicas , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Ratones Endogámicos CBA , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
We studied the state of different pools of mesenchymal precursor cells in the bone marrow, peripheral blood, and wound surface after modeling of tissue damage by skin flap removal. The participation of regional and circulating stromal precursors in the healing of skin defect and the absence of compensatory reaction of the regeneratory process deep reserve, mesenchymal stem cells of the bone marrow, was demonstrated.
Asunto(s)
Células de la Médula Ósea/fisiología , Células Madre Mesenquimatosas/fisiología , Piel/lesiones , Cicatrización de Heridas/fisiología , Animales , Células de la Médula Ósea/citología , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Femenino , Insulina , Péptidos y Proteínas de Señalización Intercelular , Masculino , Ratones , Ratones Endogámicos CBA , Estadísticas no Paramétricas , Células del Estroma/citología , Células del Estroma/fisiologíaRESUMEN
We studied changes in the erythroid hemopoietic stem during blood loss of different severity. Stimulation of erythropoiesis during the posthemorrhagic period was related to functional activation of erythroid precursors, which resulted from changes in feeder capacity of cells from the hemopoiesis-inducing microenvironment and erythropoietic activity of the plasma. The development of encephalopathy under conditions of massive blood loss was accompanied by a reduction of erythroid hyperplasia due to a decrease in the number of proliferating erythroid precursor cells, despite high secretory activity of adherent myelokaryocytes, rise in erythropoietic activity of the plasma, increased formation of erythroid hemopoietic islets, and accelerated maturation of hemopoietic cells.
Asunto(s)
Células Precursoras Eritroides/fisiología , Eritropoyesis/fisiología , Hemorragia/fisiopatología , Animales , RatonesRESUMEN
Morphological composition of the bone marrow, content of hemopoietic precursors, intensity of their proliferation and differentiation, and the size of mesenchymal precursor pool were studied in experiments on CBA/CaLac mice with myelosuppression induced by adriamycin, cyclophosphamide, or 5-fluorouracil in the maximum tolerated doses. The dynamics of changes in the content of granulomonocyte precursors in the bone marrow after cytostatic treatment was similar to that of erythroid precursors. Changes in the content of stromal mechanocytes were specific for each cytostatic. Different character of the reaction of the hemopoietic and mesenchymal stem cells to the test cytostatics was demonstrated.
Asunto(s)
Antineoplásicos/farmacología , Células de la Médula Ósea/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Células de la Médula Ósea/citología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclofosfamida/farmacología , Doxorrubicina/farmacología , Fluorouracilo/farmacología , Células Madre Hematopoyéticas/citología , Masculino , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos CBARESUMEN
We studied processes of proliferation and differentiation of hemopoietic precursor cells in mice treated with granulocyte CSF under conditions of cytostatic myelodepression. It was found that the hemostimulating effect of original granulocyte CSF preparation consists in accelerated maturation of hemopoietic precursors and increased content of DNA-synthesizing CFU-GM in the bone marrow.
Asunto(s)
Antineoplásicos/farmacología , Médula Ósea/fisiología , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Regeneración , Animales , Médula Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclofosfamida/farmacología , Cinética , Masculino , Ratones , Células MadreRESUMEN
Experiments on Wistar rats showed that cisplatin and carboplatin induced similar morphological alterations in the ovaries. Both agents reduced the number of structural and functional elements, but the effect of cisplatin was more pronounced. Morphological changes observed in the early period after injection of the preparations were accompanied by prolongation of the estrous cycle, which was longer in rats treated with carboplatin. Partial and reversible sterility was observed in females at the early terms after cisplatin treatment.
Asunto(s)
Antineoplásicos/farmacología , Carboplatino/farmacología , Cisplatino/farmacología , Ovario , Animales , Ciclo Estral/efectos de los fármacos , Femenino , Infertilidad Femenina , Ovario/citología , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Ratas , Ratas WistarRESUMEN
Single and course administration of ultralow doses of antibodies gamma-interferon did not increase the incidence of cytogenetic abnormalities in bone marrow cells from BALB/c mice and produced no genotoxic effect on Drosophila melanogaster wing cells in the test of somatic mosaicism.