RESUMEN
In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.
Asunto(s)
Betula , Colesterol , Cricetinae , Masculino , Animales , Mesocricetus , Ácidos y Sales Biliares/metabolismo , Triglicéridos , Pectinas , Hígado/metabolismo , Dieta Alta en Grasa , HecesRESUMEN
We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice. The complex reduced the genotoxic effect doxorubicin in metaphase plates of bone marrow cells in 24, 48 h, and 10 days after the administration of the cytostatic. The mean number of single fragments and the fraction of cells with gaps and aberrant metaphases also decreased.
Asunto(s)
Sorbus , Animales , Ratones , Antocianinas/farmacología , Frutas , Ratones Endogámicos C57BL , Extractos Vegetales/farmacologíaRESUMEN
We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells.
Asunto(s)
Aconitum , Células Madre Adultas , Neoplasias Mamarias Experimentales , Femenino , Ratones , Animales , Metilnitrosourea , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Células Madre Adultas/patología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patologíaRESUMEN
The results of studying the effect of the anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice with Lewis lung carcinoma against the background of doxorubicin administration were presented. It was shown that administration of the anthocyanin-containing complex from S. aucuparia L. to animals with the tumor prevented the development of anemic syndrome by promoting regeneration of the erythropoiesis after its depletion caused by single administration of a cytostatic agent.
Asunto(s)
Carcinoma Pulmonar de Lewis , Citostáticos , Sorbus , Animales , Antocianinas/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Eritropoyesis , RatonesRESUMEN
Various stem cells were studied in female BALB/c mice at the early terms after administration of N-methyl-N-nitrosourea to search early diagnostic markers and therapeutic targets. At these terms, damage to the epithelium and endothelium, inflammation, and fibrosis were observed in the mammary gland, but the tumor was not detected. Cancer stem cells, hematopoietic stem cells (HSC), hematopoietic progenitor cells, angiogenic precursors, and epithelial progenitor cells were found in the blood and mammary gland. Cancer stem cells (CD44+CD24-) are proposed as the early diagnostic marker of breast cancer, and short-living HSC, hematopoietic progenitor cells, and angiogenic precursors (CD45-CD117+FLK-1+) as predictors of the formation of tumor microenvironment.
Asunto(s)
Neoplasias de la Mama , Antígeno CD24 , Animales , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Epitelio/patología , Femenino , Células Madre Hematopoyéticas/patología , Humanos , Receptores de Hialuranos , Ratones , Células Madre Neoplásicas/patología , Microambiente TumoralRESUMEN
Analysis of specific pharmacological activity evaluated high antinociceptive efficacy of the first synthesized compound 10-di(ethoxyacetyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane (ethowurtzine) in models of somatogenic pain of different genesis (thermal, visceral pain, mechanical compression of paw).The new molecule from the class of hexaazaisowurtzitane effectively blocks nociceptive reactions at the supraspinal and peripheral levels of pain sensitivity organization. The effect of ethowurtzine was comparable or exceeded the effect of tramadol. The obtained results prove the possibility of creating new pharmacologically active molecules based on the high-energy substance hexaazaisowurtzitane.
Asunto(s)
Dolor , Tramadol , Humanos , Dimensión del Dolor/métodos , Dolor/tratamiento farmacológico , Tramadol/farmacología , Tramadol/uso terapéutico , Umbral del Dolor , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos Opioides/farmacologíaRESUMEN
We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S. aucuparia L. prevented the development of anemic syndrome by stimulating regeneration of the erythroid lineage of hematopoiesis after its devastation by single administration of the cytostatic.
Asunto(s)
Antocianinas/metabolismo , Eritropoyesis/fisiología , Anemia/genética , Anemia/metabolismo , Animales , Antocianinas/genética , Doxorrubicina/uso terapéutico , Eritropoyesis/genética , Hematopoyesis/genética , Hematopoyesis/fisiología , Masculino , Ratones Endogámicos C57BLRESUMEN
Using rat and mouse models of neurogenic, ethanol-induced, and indometacin-induced damage to the gastric mucosa we demonstrated that course preventive treatment with flavonoid complex from aerial parts of Lychnis chalcedonica L. increased the resistance of gastric mucosa to ulcerogenic factors of different etiology. The gastroprotective effect of the phytocomplex in a dose range of 16-1600 µg/kg was comparable with that of the reference drug plantaglucide and was superior to that of the reference drugs eleutherococcus extract and methyluracil in the therapeutic doses. The antiulcerogenic activity of Lychnis chalcedonica flavonoid complex considerably exceeded activity of Lychnis chalcedonica L. extract demonstrated in our previous experiments.
Asunto(s)
Antiulcerosos/uso terapéutico , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Animales no Consanguíneos , Antiulcerosos/aislamiento & purificación , Antiulcerosos/farmacología , Citoprotección/efectos de los fármacos , Modelos Animales de Enfermedad , Etanol , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Indometacina , Lychnis/química , Masculino , Ratones , Inflamación Neurogénica/tratamiento farmacológico , Inflamación Neurogénica/patología , Fitoterapia , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Silene , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
Pronounced analgesic activity of the innovative compound 4-(3,4-dibromthiophencarbonyl)-2,6,8,12-tetraacethyl-2,4,6,8,10,12hexaazatetracyclo[5,5,0,03, 11,05, 9] dodecane (thiowurtzine) was observed in the thermal nociceptive hot plate test and in the acute visceral and somatic deep pain model (acetic acid writhing test). In these experimental models, naloxone-sensitive thiowurtzine-induced analgesia was revealed. The absence of tropism to peripheral opioid receptors in the acetic acid writhing test was demonstrated using naloxone methiodide. Course administration of low-toxic thiowurtzine in effective doses was not associated with ulcerogenic damage to the gastric mucosa in experimental animals.
Asunto(s)
Analgésicos/uso terapéutico , Dolor/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Mucosa Gástrica/efectos de los fármacos , Masculino , Ratones , Naloxona/uso terapéutico , Dolor/fisiopatología , Dimensión del Dolor/métodosRESUMEN
We studied the effects of elastase, cigarette smoke extract, D-galactosamine hydrochloride, and tyrosine kinase inhibitor SU5416 on endothelial progenitor cells and angiogenesis precursors, as well as on Notch-1 expression by immature endothelial cells. Simultaneously with pulmonary emphysema, different damaging factors with diverse mechanisms of action caused pathological changes in the microvascular network of the lungs and destroyed the alveolar endothelium in female C57Bl/6 mice. D-galactosamine hydrochloride disturbed mobilization of endothelial progenitor cells expressing VEGFR (CD45-CD309+) and angiogenesis progenitors (CD45-CD309+CD117+) and their migration into emphysema expanded lungs. Elastase inhibited VEGFR-expressing endothelial progenitor cells, while cigarette smoke extract inhibited cells with CD45-CD31+CD34+ phenotype. In pulmonary emphysema provoked by elastase or D-galactosamine hydrochloride, angiogenesis was provided by endothelial cells with CD45-CD31+CD34+ phenotype, whereas in emphysema modeled with SU5416 or cigarette smoke extract, it was provided by the endothelial VEGFR-expressing cells and mature CD31+ endothelial cells, respectively. Replenishment of immature endothelial cells damaged by elastase and SU5416 involved Notch-1+ angiogenesis precursors and Notch-1+ endothelial progenitor cells with VEGFR.
Asunto(s)
Células Progenitoras Endoteliales/citología , Neovascularización Fisiológica , Enfisema Pulmonar/metabolismo , Receptor Notch1/genética , Regeneración/fisiología , Transducción de Señal , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Mezclas Complejas/aislamiento & purificación , Mezclas Complejas/toxicidad , Células Progenitoras Endoteliales/metabolismo , Endotelio/citología , Endotelio/metabolismo , Femenino , Galactosamina/toxicidad , Regulación de la Expresión Génica , Indoles/toxicidad , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Elastasa Pancreática/toxicidad , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/genética , Enfisema Pulmonar/patología , Pirroles/toxicidad , Receptor Notch1/metabolismo , Nicotiana/química , Nicotiana/toxicidad , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90+ and epithelial progenitors CD45-CD31-Sca-1+CD49f+ derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24+CD52+ had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90+ and CD117+CD90+ as well as endothelial progenitors CD45-CD31+ derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.
Asunto(s)
Células Progenitoras Endoteliales/citología , Células Madre/citología , Animales , Busulfano/farmacología , Antígeno CD24/metabolismo , Antígeno CD52/metabolismo , Células Progenitoras Endoteliales/efectos de los fármacos , Inflamación/metabolismo , Integrina alfaV/metabolismo , Masculino , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-kit/metabolismo , Espermatogénesis/efectos de los fármacos , Espermatogonias/citología , Espermatogonias/efectos de los fármacos , Células Madre/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Antígenos Thy-1/metabolismoRESUMEN
Anti-inflammatory and analgesic activities of the complex of flavonoids from Lychnis chalcedonica L. were studied in the models of acute aseptic inflammation induced by carrageenan, histamine, and serotonin and acetic acid-induced painful chemical stimulation. It is demonstrated that course treatment with flavonoids derived from Lychnis chalcedonica L. produced a stable pharmacological effect comparable with that of the reference anti-inflammatory drug diclofenac.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Carragenina/toxicidad , Flavonoides/uso terapéutico , Inflamación/tratamiento farmacológico , Lychnis/química , Ácido Acético/toxicidad , Animales , Diclofenaco/uso terapéutico , Femenino , Histamina/toxicidad , Inflamación/inducido químicamente , Masculino , Ratones , Serotonina/toxicidadRESUMEN
The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117-CD90+ and CD51-CD24+CD52+ from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45-CD31-Sca-1+CD49f+) and endothelial (CD45-CD31+) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117-CD90+ spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1+ cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in "busulfan" testes; the level of tissue testosterone and fertility index also increased.
Asunto(s)
Busulfano/toxicidad , Isquemia/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Regeneración/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatogonias/metabolismo , Animales , Antígenos CD/genética , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Expresión Génica , Isquemia/patología , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Ligadura , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Ratones , Ratones Endogámicos C57BL , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patología , Cordón Espermático/irrigación sanguínea , Cordón Espermático/cirugía , Espermatogonias/efectos de los fármacos , Espermatogonias/patología , Trasplante de Células Madre , Testosterona/biosíntesisRESUMEN
Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45(-)CD31(+)CD34(+)) and epithelial (CD45(-)CD117(+)CD49f(+)) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue. Emphysematous changes in the lungs were accompanied by infiltration of the alveolar septa with macrophages and lymphocytes, increase in the serum and lung concentrations of transforming growth factor-ß, IL-1ß, IL-2, IL-5, IL-10, and IL-13, and lung concentration of IL-17. In the lungs, inflammation was associated with marked increase in the number of multipotent mesenchymal stromal cells CD90(+)CD73(+)CD106(+)CD44(+)) and Clara cells (CD45(-)CD34(-)CD31(-)Sca1(+)) and overexpression of extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, fibronectin) and Clara cells protein. On the other hand, elastase reduced the number of angiogenic precursor cells (CD45(-)CD117(+)Flk1(+)).
Asunto(s)
Proteínas de la Matriz Extracelular/metabolismo , Inflamación/metabolismo , Células Madre/metabolismo , Animales , Células Epiteliales/metabolismo , Femenino , Células Caliciformes/metabolismo , Inmunohistoquímica , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Interleucina-2/metabolismo , Interleucina-5/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patología , Células Madre/patología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
The effects of Fructus Sorbi aucupariae extract, originally saturated with anthocyans, on the development of Lewis lung carcinoma and B-16 melanoma in C57Bl/6 mice and the efficiency of cyclophosphamide treatment were studied. Antitumor activity of the extract and potentiation of the antimetastatic activity of the cytostatic were demonstrated. Studies on melanoma B-16 model revealed an increase in the counts of stromal progenitor cells in the tumor node and their accelerated maturation after treatment with the extract. No effects towards the tumor stem and committed cells were detected.
Asunto(s)
Antocianinas/farmacología , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Fitogénicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Ciclofosfamida/farmacología , Melanoma Experimental/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma Pulmonar de Lewis/patología , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Frutas/química , Inyecciones Intramusculares , Metástasis Linfática , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Extractos Vegetales/aislamiento & purificación , Sorbus/química , Carga Tumoral/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
Stem and progenitor cells were studied on mouse model of testicular ischemia. Testicular ischemia led to a decrease in free testosterone concentration. Hemodynamic changes, interstitial edema, and destruction of spermatogenic epithelium, Leydig, and Sertoli cells were observed in the testicular tissue. Accumulation of degenerative germ cells was accompanied by reduction in the count of spermatogonial stem cells with immunophenotype CD117(-)CD29(+)CD90(+) and CD117(+)CD29(+)CD90(+). Simultaneously with pathomorphological changes in the testes and suppression of spermatogenesis, ischemia reduced the count of hematopoietic progenitor cells, hematopoietic stem cells with immunophenotype Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(+) and Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(-), and multipotent mesenchymal stromal cells (CD45(-)CD31(-) CD90(+)CD106(+)) in the testicular tissue. The population of CD45(-)CD31(+)-endothelial cells in ischemic testicular tissue increased.
Asunto(s)
Células Endoteliales/patología , Células Madre Hematopoyéticas/patología , Isquemia/patología , Células Madre Mesenquimatosas/patología , Testículo/citología , Testículo/patología , Animales , Antígenos CD34/metabolismo , Antígenos Ly/metabolismo , Diferenciación Celular/fisiología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Madre Hematopoyéticas/metabolismo , Isquemia/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-kit/metabolismo , Testículo/metabolismoRESUMEN
Mice with Lewis lung carcinoma were used to study the antitumor and antimetastatic effects of JAK3 inhibitor. The study revealed no effect of JAK3 inhibitor on the growth of primary tumor node, but found a pronounced inhibition of hematogenous spread of the pathologic process into the lungs. In vitro blockade of JAK3 in cultured Lewis lung carcinoma produced no effect on the count of the stem tumor cells and stimulated functions of committed elements. In addition, blockade of JAK3 significantly elevated maturation index of the tumor tissue.
Asunto(s)
Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/enzimología , Inhibidores Enzimáticos/uso terapéutico , Janus Quinasa 3/antagonistas & inhibidores , Animales , Inhibidores Enzimáticos/farmacología , Femenino , Ratones , Ratones Endogámicos C57BL , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismoRESUMEN
The effects of nonstarch polysaccharides with different molecular weights on the development of Lewis' lung carcinoma and efficiency of cyclophosphamide therapy in mice were studied. Treatment with these substances with low molecular weights (<30 kDa) caused no changes in the primary tumor growth, but inhibited its metastasizing, while nonstarch polysaccharides with high molecular weights (>400 kDa) inhibited the growth of Lewis' lung carcinoma node. Antimetastatic effects of cyclophosphamide were stimulated by low and high molecular weight polysaccharides.
Asunto(s)
Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Polisacáridos/uso terapéutico , Animales , Carcinoma Pulmonar de Lewis/patología , Sinergismo Farmacológico , Femenino , Ratones , Ratones Endogámicos C57BL , Peso MolecularRESUMEN
The effects of various alginate forms on the development of transplanted tumors in mice and efficiency of cytostatic therapy were studied. High-molecular-weight Ca and Na alginates, acid-soluble hydrolysate, and sodium alginate fraction inhibited the growth of Ehrlich adenocarcinoma. The use of acid-insoluble sodium alginate in chemotherapy protocol improved the treatment efficiency. All alginate forms inhibited metastasizing of Lewis pulmonary carcinoma; in combination with cyclophosphamide they potentiated its antimetastatic effect.