RESUMO
Immunohistochemical detection of the LYVE-1 marker in healthy human full-thickness skin (the epidermis and the dermis) was carried out. LYVE-1 expression was found in the endothelium of lymphatic capillaries located in the papillary dermis, in the endothelium of larger lymphatic vessels of the reticular dermis, and in fibroblasts, which indicates their joint participation in hyaluronan metabolism. LYVE-1+ staining detected for the first time in cells of the stratum basale, the stratum spinosum, and the stratum granulosum of healthy human epidermis indicates their participation in hyaluronan metabolism and allows us to consider the spaces between epidermis cells as prelimphatics.
Assuntos
Epiderme , Ácido Hialurônico , Vasos Linfáticos , Pele , Proteínas de Transporte Vesicular , Humanos , Ácido Hialurônico/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/genética , Pele/metabolismo , Vasos Linfáticos/metabolismo , Epiderme/metabolismo , Ligantes , Fibroblastos/metabolismo , Derme/metabolismo , Sistema Linfático/metabolismo , Adulto , Feminino , Masculino , Imuno-HistoquímicaRESUMO
Continuous lighting for 14 days (functional pinealectomy model) leads to a decrease in the relative number of CD3low and CD3hi T lymphocytes and the CD3low/CD3hi ratio in the thymus of C57BL/6 mice. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight, 14 days) against the background of functional pinealectomy restores the percentage of CD3low and CD3hi thymocytes and CD3low/CD3hi ratio to the control values. Hence, prolonged continuous illumination inhibits the differentiation and maturation of young thymocytes into mature forms, while melatonin treatment helps to compensate the effects of functional pinealectomy triggering cell proliferation in the thymus from the earliest stages of proliferation and differentiation of T cells. Thus, melatonin has immunotropic properties and can be used for correction of the consequences of functional pinealectomy.
Assuntos
Melatonina , Glândula Pineal , Animais , Camundongos , Complexo CD3 , Melatonina/farmacologia , Camundongos Endogâmicos C57BL , Glândula Pineal/fisiologia , Glândula Pineal/efeitos da radiação , Pinealectomia , TimoRESUMO
Light-induced functional pinealectomy was simulated in C57BL/6 mice by 14-day exposure to constant lighting. Immunophenotyping of CD3hi and CD3low thymocytes was performed by staining with CD3-APC antibodies followed by flow cytofluorometry. To study the cell cycle distribution of thymus cells, the content of intracellular DNA was measured by the level PI inclusion. In animals with light-induced functional pinealectomy, blood leukocyte content, the relative number of CD3low and CD3hi T cells in the thymus, and the ratio of CD3low/CD3hi thymocytes decreased. The number of G0/G1-phase thymus cells (non-dividing cells) increased and the content of S-phase cells (division phase) decreased. Continuous lighting stimulated the development of thymocyte apoptosis. The results obtained indicate that prolonged 24-h illumination inhibits differentiation and maturation of young CD3low thymocytes into mature CD3hi forms and leads to the development of T-cell apoptosis in the thymus and, as a consequence, to leukopenia.
Assuntos
Pinealectomia , Timo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Timo/patologia , Timo/fisiologia , Pinealectomia/efeitos adversosRESUMO
We performed an immunohistochemical study of MT2 melatonin receptor expression in the liver of C57BL/6 mice with modeled light-induced functional pinealectomy and after melatonin administration by the indirect avidin-biotin peroxidase ABC method. The animals were kept for 14 days under constant lighting. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight for 14 days) to mice with light-induced functional pinealectomy resulted in a 2-fold increase in the relative expression area of MT2 receptors in liver cells in comparison with that in animals kept under standard lighting conditions, 24-h lighting for 14 days, or 24-h lighting receiving placebo (intragastric administration of 200 ml distilled water). Melatonin treatment had practically no effect on MT2 staining intensity. Our results attest to the important role of MT2 receptors in melatonin synthesis disorders and can serve as the basis for the development of therapeutic strategies aimed at melatonin receptors.
Assuntos
Melatonina , Animais , Avidina , Biotina , Fígado/metabolismo , Fígado/cirurgia , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Peroxidases , Pinealectomia , Receptor MT1 de Melatonina/genética , Receptores de Melatonina , ÁguaRESUMO
Intragastric administration of melatonin in physiological doses (1 mg/kg body weight) for 14 days to C57BL/6 mice with light-induced functional pinealectomy model (24-h lighting for 14 days) results in an increase in the LYVE-1 expression area by 2.4 times and a significant increase in receptor concentration (1.6% decrease in staining brightness) in liver sinusoidal endothelial cells in comparison with animals kept under continuous lighting and not treated with the hormone, which indicates the formation of stability of the endothelial barrier in the organ. Melatonin treatment also enhanced lymphatic drainage in all it links (including interstitial non-vascular pathways and lymphatic vessels) and improved structural and functional parameters of blood circulation and lymph flow in the organ, which created conditions for reducing metabolic load on structural elements of the liver.
Assuntos
Melatonina , Animais , Células Endoteliais/metabolismo , Glicoproteínas/metabolismo , Fígado/metabolismo , Fígado/cirurgia , Melatonina/metabolismo , Melatonina/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , PinealectomiaRESUMO
The presence of humans and animals under long-term continuous lighting leads to a suppression of melatonin synthesis, that is, to light-induced functional pinealectomy (LIFP), and the development of desynchronosis. To create LIFP, C57Bl/6 mice were kept under 24-hour lighting (24hL) for 14 days. The animals in the control group were kept under standard lighting conditions. In the next series of experiments, mice with LIFP received daily intragastrically either melatonin (1 mg/kg body weight in 200 µl of distilled water) or 200 µl of water as a placebo. The comparison group consisted of intact animals that received placebo under standard lighting conditions. Immunohistochemical analysis (using an indirect avidin-biotin peroxidase method) revealed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in sinusoid liver cells (a heterogeneous population consisting of the endotheliocytes, Kupffer cells, Ito cells, and Pit cells) and in individual hepatocytes. The Bad expression area in the liver of LIFP mice increased 4 times against a background of the unchanged Bcl-2 expression area. Changes in the brightness (a parameter inversely proportional to the marker concentration) of Bad and Bcl-2 areas did not reach significance. Our results indicate a weakening of the antiapoptotic protection of liver cells of LIFP animals, which creates conditions for activation of the "mitochondrial branch" of apoptosis. Melatonin treatment of LIFP mice resulted in a 3.3-fold increase in Bcl-2 expression area and a 2.7 % decrease in Bcl-2 region brightness compared with the experimental untreated group. Bad protein parameters were unreliable. Thus, melatonin treatment of animals cancels the effect of LIFP, restoring the Bcl-2 expression area and increasing this protein concentration, which indicates an increase in antiapoptotic protection and creates conditions for blocking the development of the "mitochondrial branch" of apoptosis in liver cells.
RESUMO
Expression of proapoptotic Bad and antiapoptotic Bcl-2 proteins in ovarian follicular apparatus of Wistar rats was evaluated on days 3, 7, and 14 after single experimental hyperthermia (EH) followed by therapeutic correction with subcutaneous melatonin (0.1 mg) dissolved in 0.2 ml physiological saline (PS) injected daily for 3 days. Duration of EH was less than 17 min; it was terminated when the rectal temperature attained 43.5°C. In acute posthyperthermia period (on experimental day 3), Bcl-2 and Bad expression area in folliculocytes of the experimental (EH+melatonin) and reference rats simultaneously increased in comparison with the corresponding values in control rats. At this, Bcl-2/Bad ratio of expression areas in experimental and reference rats did not differ from the control level. During the recovery period (on posthyperthermia day 7), Bad protein expression area significantly decreased in experimental rats resulting in elevation of Bcl-2/Bad ratio in comparison with control and reference groups on days 3 and 7. On day 14, Bcl-2 and Bad expression areas and Bcl-2/Bad ratio restored in experimental animals to the corresponding values assessed in control and reference groups. Thus, melatonin produced no effect on Bcl-2/Bad protein expression ratio during acute posthyperthermia period, but reduced the expression area of proapoptotic Bad protein and increased Bcl-2/Bad ratio on posthyperthermia day 7. Thus, melatonin can inhibit apoptosis via mitochondrial pathway in ovarian follicles on posthyperthermia day 7.
Assuntos
Melatonina/farmacologia , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Animais , Apoptose/efeitos dos fármacos , Feminino , Hipertermia Induzida , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Folículo Ovariano/efeitos dos fármacos , Ratos Wistar , TemperaturaRESUMO
Obesity and diabetes mellitus are known to lead to the development of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). The mechanisms of programmed cell death are actively involved in maintaining cellular homeostasis along development of NAFLD. Proteins of the BCL-2 family are key regulators of physiological and pathological apoptosis. Homozygous males of BKS.Cg-Dock7mLeprdb/+/+/J mice (db/db mice) are characterized by progressive obesity and the development of type 2 diabetes mellitus (DM2) with severe hyperglycemia at 4-8 weeks and organ lesions at 8-10 weeks of age. The aim of this research was to study the expression of molecular cell regulators of apoptosis in liver cells of db/db mice males at different stages of obesity and diabetes development (at the age of 10 and 18 weeks). Immunohistochemical analysis (using the indirect avidin-biotin peroxidase method) and morphometric evaluation of the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in liver cells of studied animals at different stages of obesity and DM2 were carried out. An excess of the value of the Bcl-2 protein staining area over the Bad protein staining area was revealed in the liver of 10-week-old animals. The Bcl-2/Bad expression area ratio in 10-week-old animals was twice as high as in 18-week-old animals, which indicates the presence of conditions for blocking apoptosis in the liver of younger db/ db mice. At the 18th week of life, db/db mice displayed an almost threefold increase in the expression area of the Bad protein against the background of an unchanged expression of the Bcl-2 protein. The decrease in the Bcl-2/Bad staining area ratio in 18-week-old animals was due to the increase in the Bad expression area, which indicates the absence of antiapoptotic cell protection and creates conditions for activation of the mitochondrial pathway of apoptosis in the liver of male db/db mice with pronounced signs of obesity and DM2.
RESUMO
The expression of molecular and cellular regulators of apoptosis (proapoptotic protein Bad and antiapoptotic protein Bcl-2) was measured in the follicular apparatus of rat ovaries during the recovery period (days 7 and 14) after hyperthermia (up to rectal temperature 43.5°C). The Bcl-2/Bad index was calculated. The expression of Bcl-2 in the follicular apparatus of rat ovaries increased on day 7 after the exposure. The Bcl-2/Bad index also increased, which suggests that the development of apoptosis by the mitochondrial pathway in follicles was limited at this term after hyperthermia. On day 14 after hyperthermia, the area of immunohistochemical staining for the antiapoptotic protein Bcl-2 significantly decreased in cells of the ovarian follicular epithelium, but the expression of the proapoptotic protein Bad significantly increased; these changes led to a decrease in Bcl-2/Bad index, which attested to weakening of the antiapoptotic defense and activation of oocyte apoptosis by the mitochondrial pathway.
Assuntos
Hipotermia/patologia , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Recuperação de Função Fisiológica/fisiologia , Proteína de Morte Celular Associada a bcl/biossíntese , Animais , Apoptose/fisiologia , Feminino , Mitocôndrias/metabolismo , Ratos , Ratos WistarRESUMO
Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group. Studies by the low-field NMR spectrometry detected lower lean body mass, total body water, and especially, fat content (by ~13%) in animals receiving placebo. Melatonin treatment led to an increase in the lean body mass and total body water on day 7 (in comparison with the placebo group) without affecting fat mass. On day 14 of continuous illumination, lean body mass increased in comparison with the corresponding parameter in the control and placebo groups. Melatonin had no effect on the physical endurance of mice exposed to continuous illumination (assessed by the grid hanging test).
Assuntos
Composição Corporal/efeitos da radiação , Eritrócitos/efeitos dos fármacos , Eritrócitos/efeitos da radiação , Luz , Melatonina/farmacologia , Animais , Composição Corporal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , FotoperíodoRESUMO
We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin on the expression of apoptosis regulator proteins Bcl-2 and Bad in the liver of db/db mice with genetically determined obesity and type 2 diabetes mellitus. The mice received daily linagliptin or saline (placebo) by gavage from week 10 to week 18 of life. In the liver of non-treated mice, the area positively stained for Bad was greater than the area of Bcl-2 expression, which created the conditions for apoptosis activation in liver at this age. Administration of linagliptin decreased Bad stained area and increased Bcl-2 stained area in the liver cells. At the same time, Bad stained area remained larger in treated mice than the area of Bcl-2 expression area, which attested to partial normalization of pro- and antiapoptotic protein balance.
Assuntos
Linagliptina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Fígado , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia.
Assuntos
Hipertermia Induzida/métodos , Folículo Ovariano/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Proteína de Morte Celular Associada a bcl/genética , Animais , Apoptose/genética , Diestro/fisiologia , Feminino , Regulação da Expressão Gênica , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Folículo Ovariano/citologia , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/agonistas , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
The effects of various treatment modes on the morphology of anterior mediastinal lymph nodes were examined in female Wistar rats with chemically provoked breast cancer. Adjuvant chemotherapy impaired filtration barrier potential of the anterior mediastinal lymph nodes, which manifested in increased volume of sinuses, reduced volumes of lymphoid nodules with germinal centers and thymus-dependent regions, down-regulated proliferative activity of lymphoid cells in B-cell zone and paracortex, and diminished macrophage score in all zones. Intraperitoneal injection of double-stranded DNA preparation (5 mg/kg) activated the humoral and cellular immune responses manifested by morphological alterations in anterior mediastinal lymph nodes observed in parallel with a decrease of medullary sinuses volume: enhancement of lymphocyte volume and lymphocyte score in paracortex, mantle zone expansion, and an increase of volume of the light centers in lymphoid nodules paralleled with diminished proliferative activity in them.
Assuntos
Linfonodos/metabolismo , Neoplasias Mamárias Animais/imunologia , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/metabolismo , Animais , Linfócitos B/metabolismo , DNA/genética , DNA/fisiologia , Feminino , Imunidade Celular/genética , Imunidade Celular/fisiologia , Imunidade Humoral/genética , Imunidade Humoral/fisiologia , Ratos , Ratos WistarRESUMO
We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Melatonina/farmacologia , Obesidade/tratamento farmacológico , Substâncias Protetoras/farmacologia , Óxido de Alumínio/química , Animais , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Homozigoto , Fígado/metabolismo , Fígado/patologia , Melatonina/química , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Silicones/química , Proteína de Morte Celular Associada a bcl/antagonistas & inibidores , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
The anterior mediastinal lymph nodes were analyzed morphometrically in rats with chemically provoked breast cancer. Rats with untreated breast cancer and animals receiving chemotherapy demonstrated decreased volumes of paracortical region and lymphoid nodules with the germinal centers accompanied by extended medullary thymic substance. Resection of largest focus of breast tumor improved the filtration barrier potential of anterior mediastinal lymph nodes, up-regulated the proliferative activity of lymphoid cells in T-cell zones, and down-regulated proliferation of plasmatic cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linfonodos/patologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/patologia , Mediastino/patologia , Animais , Carcinógenos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Ciclofosfamida/farmacologia , Feminino , Fluoruracila/farmacologia , Injeções Subcutâneas , Linfonodos/efeitos dos fármacos , Linfonodos/cirurgia , Metástase Linfática , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/cirurgia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/cirurgia , Mediastino/cirurgia , Metotrexato/farmacologia , Metilnitrosoureia/administração & dosagem , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Ratos , Ratos Wistar , Linfócitos T/efeitos dos fármacos , Linfócitos T/patologiaRESUMO
Morphological changes in the thymus of female Wistar rats with experimental mammary gland carcinomas were studied. After adjuvant therapy, the area of the cortical matter and density of parenchymal cells in the thymus decreased, while areas of the medulla, connective tissue, and content of immunoblasts and macrophages increased. In the thymuses of rats receiving exogenous DNA, morphological signs of activation of the lymphoid and epithelial components were found: areas of the cortex and medulla, glandular and connective tissue corresponded to the values in intact animals, the counts of lymphocytes in the central part of the cortical matter and of macrophages in all zones of the thymus increased, and lymphocyte migration from the thymus increased (in comparison with the chemotherapy group).
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Mamárias Experimentais/terapia , Timo/patologia , Animais , Terapia Combinada , Feminino , Humanos , Mastectomia , Ratos Wistar , Timo/efeitos dos fármacosRESUMO
Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus. Animals of the experimental tumor+chemotherapy group exhibited morphological signs of lymphocyte migration from the thymus and suppressed activities of the lymphoid and epithelial components (lesser area of connective tissue elements and glandular tissue, lesser density of parenchymatous cell elements, lesser counts of immunoblasts and small lymphocytes, and larger area of the medulla) in comparison with animals without chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinogênese/efeitos dos fármacos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Timo/efeitos dos fármacos , Neoplasias do Timo/tratamento farmacológico , Animais , Carcinógenos/toxicidade , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Ciclofosfamida/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Fluoruracila/administração & dosagem , Injeções Intraperitoneais , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metotrexato/administração & dosagem , Metilnitrosoureia/toxicidade , Ratos Wistar , Timo/patologia , Neoplasias do Timo/secundárioRESUMO
The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicoproteínas/agonistas , Hiperglicemia/tratamento farmacológico , Melatonina/farmacologia , Obesidade/tratamento farmacológico , Óxido de Alumínio/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Glicoproteínas/metabolismo , Artéria Hepática/efeitos dos fármacos , Artéria Hepática/metabolismo , Artéria Hepática/patologia , Homozigoto , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Proteínas de Membrana Transportadoras , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Silicones/químicaRESUMO
We studied the effect 24-h illumination on quantitative and qualitative parameters of the bone marrow cells in Wistar rats. It was shown that desynchronosis reduced the release of nucleated cells from the femoral bone, while melatonin weakened this effect. The number of bone marrow mesenchymal stromal cells was resistant to circadian rhythm disturbances, while proliferation depended on glucose concentration in the medium.
Assuntos
Células da Medula Óssea/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células-Tronco Mesenquimais/efeitos da radiação , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Meios de Cultura/farmacologia , Glucose/metabolismo , Glucose/farmacologia , Luz , Masculino , Melatonina/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fotoperíodo , Ratos , Ratos WistarRESUMO
Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action.