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1.
Int. j. morphol ; 38(4): 1032-1038, Aug. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1124893

RESUMO

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.


El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.


Assuntos
Animais , Dexametasona/farmacologia , Sistema Imunitário/efeitos dos fármacos , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Galinhas , Cloaca/efeitos dos fármacos
2.
PLoS One ; 15(7): e0235476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609751

RESUMO

To explore the molecular mechanism of the effect of Bacillus cereus PAS38 on the immunity of broilers, sixty 7-day-old broilers were divided into two groups with three replicates. The control group was fed with basal diet, and the treatment group was fed with basal diet containing Bacillus cereus PAS38 1×106 CFU/g. Thymus and bursa of fabricius were taken from two groups of broilers at the age of 42 days, total RNA was extracted, differential gene library was constructed by SSH technology, and immune-related differential genes were screened. Then, we used siRNA to interfere with the expression of some differential genes in the original generation lymphocytes of broiler blood to detect the change of cytokines mRNA expression level. A total of 42 immune-related differentially expressed genes were screened, including 22 up-regulated genes and 20 down-regulated genes. When 7 differentially up-regulated genes associated with enhanced immune function were interfered with in lymphocytes, some immune-promoting cytokines were down-regulated. These results showed that Bacillus cereus PAS38 might up-regulate the expression of JCHAIN, PRDX1, CD3E, CDK6 and other genes in immune organs of broilers, thereby affecting the development of immune organs, the expression of various cytokines and the transduction of immune signals, improving the immune capacity of broilers.


Assuntos
Bacillus cereus/imunologia , Bolsa de Fabricius , Galinhas , Interações entre Hospedeiro e Microrganismos/imunologia , Probióticos/farmacologia , Timo , Animais , Bolsa de Fabricius/efeitos dos fármacos , Bolsa de Fabricius/imunologia , Galinhas/imunologia , Galinhas/microbiologia , Citocinas/genética , Citocinas/imunologia , Técnicas de Hibridização Subtrativa/métodos , Timo/efeitos dos fármacos , Timo/imunologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-32330807

RESUMO

Honey-processed Astragalus is a dosage form of radix Astragali processed with honey, which is deemed to contain better qi-tonifying effects in traditional Chinese medicine theroy. Our previous study has demonstrated that honey-processed Astragalus exhibited a better effect on reinforcing qi (vital energy) and immune improvement toward spleen qi deficiency compared with radix Astragali. However, the detailed mechanisms related to qi-tonifying effects of honey-processed Astragalus is still unclear. In this study, we evaluated the qi-tonifying effects of honey-processed Astragalus on spleen qi deficiency rats and predicted the mechanisms by aggregating metabonomics, lipidomics and network pharmacology. The results revealed that body weights, symptom scores, the levels of red blood cell, white blood cell, lymphocyte, spleen and thymus indexes, and three cytokines (TNF-α, IL-6, IFN-γ) in honey-processed Astragalus treated rats were improved in comparison with spleen qi deficiency rats. In parallel, based on the 26 biomarkers screened in metabonomics and lipidomics, we inferred that glycerophospholipid metabolism significantly regulated in pathway analysis was connected with qi-tonifying effects. Moreover, the network pharmacology analysis concluded that the compounds targets of honey-processed Astragalus CDK2, NOS3, MAPK14, PTGS1 and PTGS2 interacted with markers targets PLA2G(s) family and LYPLA1 could be responsible for regulation of glycerophospholipid metabolism to develop qi-tonifying effects. What's more, the above processes were possibly through VEGF signaling and MAPK signaling pathways.


Assuntos
Astrágalo (Planta)/química , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas em Tandem/métodos , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Composição de Medicamentos/métodos , Eritrócitos/efeitos dos fármacos , Feminino , Mel , Humanos , Leucócitos/efeitos dos fármacos , Lipidômica , Linfócitos/efeitos dos fármacos , Qi , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
5.
Am J Physiol Endocrinol Metab ; 318(5): E646-E654, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125882

RESUMO

Mouse models with lifelong inactivation of estrogen receptor-α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other nonskeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAGG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAGG-Cre-ERαflox/flox (inducible ERαKO) compared with ERαflox/flox (control) mice. 17ß-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area, and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared with control mice on BV/TV (-67%), uterine weight (-94%), thymus weight (-70%), and gonadal fat mass (-94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared with control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERα during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all, tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Útero/efeitos dos fármacos , Animais , Osso e Ossos/metabolismo , Receptor alfa de Estrogênio/genética , Feminino , Camundongos , Camundongos Transgênicos , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Timo/efeitos dos fármacos , Timo/metabolismo , Útero/metabolismo
6.
Life Sci ; 248: 117457, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32092334

RESUMO

AIMS: Multiple surgical procedures and anesthesia increase the risk of the development in children. However, the influence of such exposures on the developing childhood immunity organs is rarely reported. MATERIALS AND METHODS: High-throughput sequencing of T-cell receptor (TCR) repertoires (TCRseq) from rhesus monkeys' thymus was performed to investigate whether anesthetics could induce de novo antigen recognition via TCR or TCR development impairments. KEY FINDINGS: No significant difference between sevoflurane and control groups regarding VJ gene combinations and diversity of V and J gene was seen, nor was there an obvious change in similar average number of Complementarity Determining Region 3 (CDR3) aa clonotypes. Our analysis of Rank abundance, Gini coefficient, Simpson index, Normalized Shannon Diversity Entropy (NSDE), Morisita-Horn Similarity Index (MHSI) and Bhattacharyya Distance (BD) indicated there is no difference in TCR diversity and similarity. SIGNIFICANCE: These results suggest early events in thymic T cell development and repertoire generation are not abnormality after multiple sevoflurane exposure during childhood. The stabilization of the immune repertoires suggested the safety of sevoflurane in host immune response in children.


Assuntos
Anestésicos Inalatórios/farmacologia , Regiões Determinantes de Complementaridade/genética , Receptores de Antígenos de Linfócitos T/genética , Sevoflurano/farmacologia , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Regiões Determinantes de Complementaridade/classificação , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Macaca mulatta , Masculino , Receptores de Antígenos de Linfócitos T/classificação , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Timo/citologia , Timo/imunologia , Recombinação V(D)J/imunologia
7.
Food Chem Toxicol ; 136: 111114, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31904477

RESUMO

Perfluorooctanoic acid (PFOA) is a per- and polyfluoroalkyl substance (PFAS) once used as a surfactant in the polymerization of chemicals. Because of its ubiquitous nature and long half-life, PFOA is commonly detected in the environment, wildlife, and humans. While skin exposure to PFOA is of concern, studies evaluating the immunotoxicity of dermal exposure are lacking. These studies evaluated the immunotoxicity of PFOA (0.5-2% w/v, or 12.5-50 mg/kg/dose) following dermal exposure using a murine model. PFOA (0.5-2%) was not identified to be an irritant or sensitizer using the local lymph node assay. The IgM antibody response to sheep red blood cell. was significantly reduced in the spleen following 4-days of dermal exposure (2%). PFOA exposure produced a significant decrease in thymus (1 and 2%) and spleen (0.5-2%) weight along with an increase in liver weight (0.5-2%). Immune cell phenotyping identified a reduction in the frequency (1 and 2%) and number (0.5-2%) of splenic B-cells. To further define the mechanism of immunotoxicity, gene expression was also evaluated in the skin. The findings support a potential involvement of the nuclear receptor PPARα. These results demonstrate that dermal exposure to PFOA is immunotoxic and raise concern about potential adverse effects from dermal exposure.


Assuntos
Alérgenos/toxicidade , Caprilatos/imunologia , Caprilatos/toxicidade , Fluorcarbonetos/imunologia , Fluorcarbonetos/toxicidade , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Formação de Anticorpos , Caprilatos/administração & dosagem , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Feminino , Fluorcarbonetos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Ovinos , Pele/efeitos dos fármacos , Pele/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
8.
Nanotoxicology ; 14(3): 372-387, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31909648

RESUMO

The annual increase in the production and the use of engineering quantum dots (QDs) have led to concern about exposure and safety of QDs. To resolve the risk of Cd release from QDs, a series of Cd-free QDs, represented by CuInS2/ZnS QDs, has been developed in recent years. However, the toxicological profile of CuInS2/ZnS QDs has not been fully elucidated, especially, their immunotoxicity. Here, we performed a detailed in vitro cytotoxicity study on PEGylated CuInS2/ZnS QDs using the DC2.4 cell line and investigated their in vivo immunotoxicity using BALB/c mice. In vitro experiments showed that CuInS2/ZnS QDs were taken up by cells, promoted cell viability, enhanced release of tumor necrosis factor-α, and decreased the level of interleukin (IL)-6 in response to lipopolysaccharide stimulation. More than 5000 genes at the transcriptome level were observed by high-throughput RNA sequencing after CuInS2/ZnS QD exposure. In vivo study showed that CuInS2/ZnS QDs increased the levels of IL-4 on day 1 and enhanced the levels of IL-10 and IL-13 on day 28 in mice. There was no obvious difference in the number of spleen-derived lymphocytes, organic index, hematology and immune organ histology on days 1 and 28 after treatment. These findings demonstrated that PEGylated CuInS2/ZnS QDs disturbed the function of DC2.4 immune cells in vitro, but caused no obvious toxicity to immune system in vivo, suggesting that PEGylated CuInS2/ZnS QDs are biocompatible and have potential for bioapplication in the future.


Assuntos
Cobre/toxicidade , Sistema Imunitário/efeitos dos fármacos , Índio/toxicidade , Polietilenoglicóis/química , Pontos Quânticos/toxicidade , Sulfetos/toxicidade , Compostos de Zinco/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Sistema Imunitário/imunologia , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pontos Quânticos/química , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Transcriptoma/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
9.
Bull Exp Biol Med ; 168(3): 352-355, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31938904

RESUMO

Neuronal factor semaphorin-3A is viewed as immune suppressant of peripheral T lymphocytes, but it can also negatively affect activity of the thymus, the central organ of the immune system. The study examined the effects of this factor on proliferative activity and apoptosis of mouse thymocytes in vitro. Semaphorin-3A inhibited spontaneous and mitogen-stimulated proliferative activity of thymocytes producing no effect on the development of apoptosis in these cells. Flow cytometry revealed expression of semaphorin-3A receptors neuropilin-1 and plexin-A1 on thymocyte membranes. Approximately 13% thymocytes simultaneously expressed both receptors. The study suggests that semaphorin-3A, which is constitutively synthesized in thymic stroma in vivo, can play the role of inhibitory factor during thymocyte maturation.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Semaforina-3A/farmacologia , Timócitos/citologia , Timócitos/efeitos dos fármacos , Animais , Citometria de Fluxo , Masculino , Camundongos , Timo/citologia , Timo/efeitos dos fármacos
10.
J Vet Med Sci ; 82(3): 360-372, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-31983703

RESUMO

Neonicotinoid pesticides (NNs) act as agonists on nicotinic acetylcholine receptors (nAChRs) of insects, and there have been concerns about the effects of NNs on the health of mammals. Since nAChRs are expressed in immune cells, it is possible that NNs disturb the immune system. However, few reports have examined the immunotoxicity of clothianidin (CLO), a widely-used NN. Here, we report the effects of CLO on immune organs and type IV allergic reactions in ear auricles. We orally administered CLO at 0, 30 and 300 mg/kg/day (CLO-0, 30 and 300) to Sprague-Dawley rats for 28 days. The effects were evaluated by organ and body weights, histopathology, and immunohistochemistry (TCRαß, CD4, CD8, CD11b, CD68, CD103). In addition, some cecal contents were subjected to preliminary gut microbiota analysis, because microbiota contribute to host homeostasis, including the immunity. Our results showed loose stool, suppression of body weight gain, significant changes in organ weights (thymus: decreased; liver: increased) and changes of the gut microbiota in the CLO-300 group. There were no obvious histopathological changes in immune organs. Granulomas of the ear auricles were found in one rat of each of the CLO-30 and 300 groups, but CLO had no apparent effect on the thickness or immunohistochemistry in the ear auricles. We present new evidence that CLO affects the thymus and intestine, and might enhance the local inflammatory response. These findings should contribute to the appropriate evaluation of the safety of NNs in the future.


Assuntos
Guanidinas/toxicidade , Sistema Imunitário/efeitos dos fármacos , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Tiazóis/toxicidade , Administração Oral , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Granuloma/induzido quimicamente , Guanidinas/administração & dosagem , Hipersensibilidade Tardia/induzido quimicamente , Imuno-Histoquímica , Inseticidas/administração & dosagem , Masculino , Neonicotinoides/administração & dosagem , Agonistas Nicotínicos , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Tiazóis/administração & dosagem , Timo/efeitos dos fármacos
11.
Autoimmun Rev ; 19(3): 102468, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927086

RESUMO

In western countries, the slope of autoimmune disease (AD) incidence is increasing and affects 5-8% of the population. Mainly prevalent in women, these pathologies are due to thymic tolerance processes breakdown. The female sex hormone, estrogen, is involved in this AD female susceptibility. However, predisposition factors have to act in concert with unknown triggering environmental factors (virus, microbiota, pollution) to initiate AD. Individuals are exposed to various environmental compounds that display endocrine disruption abilities. The cellular effects of some of these molecules may be mediated through the aryl hydrocarbon receptor (AhR). Here, we review the effects of these molecules on the homeostasis of the thymic cells, the immune tolerance intrinsic factors (transcription factors, epigenetic marks) and on the immune tolerance extrinsic factors (microbiota, virus sensibility). This review highlights the contribution of estrogen and endocrine disruptors on the dysregulation of mechanisms sustaining AD development.


Assuntos
Doenças Autoimunes/imunologia , Disruptores Endócrinos/efeitos adversos , Estrogênios/imunologia , Tolerância Imunológica , Timo/efeitos dos fármacos , Feminino , Humanos , Receptores de Hidrocarboneto Arílico
12.
Food Chem Toxicol ; 136: 110954, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707033

RESUMO

Due to the growing number of applications of cadmium oxide nanoparticles (CdO NPs), there is a concern about their potential deleterious effects. The objective of our study was to investigate the effect of CdO NPs on the immune response, renal and intestine oxidative stress, blood antioxidant defence, renal fibrotic response, bone density and mineral content. Six-week-old female ICR mice were exposed to CdO NPs for 6 weeks by inhalation (particle size: 9.82 nm, mass concentration: 31.7 µg CdO/m3, total deposited dose: 0.195 µg CdO/g body weight). CdO NPs increased percentage of thymus CD3e+CD8a+ cells and moderately enhanced splenocyte proliferation and production of cytokines and chemokines. CdO NPs elevated pro-fibrotic factors (TGF-ß2, α-SMA and collagen I) in the kidney, and concentrations of AGEs in the intestine. The ratio of GSH and GSSG in blood was slightly reduced. Exposure to CdO NPs resulted in 10-fold higher Cd concentration in tibia bones. No differences were found in bone mass density, mineral content, bone area values, bone concentrations of Ca, P, Mg and Ca/P ratio. Our findings indicate stimulation of immune/inflammatory response, oxidative stress in the intestine, starting fibrotic response in kidneys and accumulation of CdO NPs in bones of mice.


Assuntos
Compostos de Cádmio/toxicidade , Fibrose/induzido quimicamente , Imunidade Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Óxidos/toxicidade , Tíbia/efeitos dos fármacos , Administração por Inalação , Animais , Compostos de Cádmio/administração & dosagem , Citocinas/metabolismo , Feminino , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Linfonodos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos ICR , Óxidos/administração & dosagem , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
13.
Life Sci ; 240: 117078, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759041

RESUMO

AIM: The cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development. MAIN METHODS: Mice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults). KEY FINDINGS: Plasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides. SIGNIFICANCE: The additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Sistema Imunitário/efeitos dos fármacos , Inseticidas/toxicidade , Maneb/toxicidade , Praguicidas/antagonistas & inibidores , Praguicidas/toxicidade , Pirazóis/toxicidade , Tiroxina/metabolismo , Tiroxina/uso terapêutico , Zineb/toxicidade , Animais , Peso Corporal , Feminino , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Análise de Sobrevida , Timo/citologia , Timo/efeitos dos fármacos , Timo/imunologia
14.
Planta Med ; 86(2): 160-168, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745939

RESUMO

This study investigated the effect of hawthorn (Crataegus monogyna) phenolic extract on lymphocyte subsets in the lymphoid organs in nonimmunized mice and on humoral immune response in sheep red blood cell-immunized mice. Hawthorn phenolic extract (50, 100, 200 mg/kg) was administered orally five or ten times. Sheep red blood cells were injected 24 h after administration of the last extract dose. The lymphocyte subsets were assessed 24 and 72 h after the last dose. Humoral immune response was determined 4 and 7 days after immunization. Five doses of the extract decreased the percentage of CD4-CD8- and CD4+ thymocytes but elevated the percentage of CD4+CD8+ and CD8+ thymic cells. The extract increased the total number, percentage, and absolute count of T and B splenocytes. When administered five times, it lowered the percentage of T lymphocytes, but boosted the population of B lymphocytes of mesenteric lymph nodes (after 24 h). However, a rise in the population of T lymphocytes was observed 72 h after five and ten doses. The extract administered ten times elevated the number of plaque-forming cells and total anti-sheep red blood cell hemagglutinin titer but reduced the 2-ME-resistant antibody titer (day 7). At the same time, five doses of the extract increased antibody titers. Considering its impact on lymphocyte subsets and humoral immune response, hawthorn extract may be used as an immunomodulator.


Assuntos
Crataegus/química , Imunidade Humoral/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Linfonodos/efeitos dos fármacos , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fenóis/isolamento & purificação , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
15.
Chemosphere ; 238: 124647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31466007

RESUMO

Ground water arsenic contamination is a global menace. Since arsenic may affect the immune system, leading to immunesuppression, we investigated the effects of acute arsenic exposure on the thymus and spleen using Swiss albino mice, exposed to 5 ppm, 15 ppm and 300 ppm of sodium arsenite for 7 d. Effects on cytokine balance and cell survivability were subsequently analyzed. Our data showed that arsenic treatment induced debilitating alterations in the tissue architecture of thymus and spleen. A dose-dependent decrease in the ratio of CD4+-CD8+ T-cells was observed along with a pro-inflammatory response and redox imbalance. In addition, pioneering evidences established the ability of arsenic to induce an up regulation of Hsp90, eventually resulting in stabilization of its client protein Beclin-1, an important autophagy-initiating factor. This association initiated the autophagic process, confirmed by co-immunoprecipitation assay, acridine orange staining and Western blot, indicating the effort of cells trying to survive at lower doses. However, increased arsenic assault led to apoptotic cell death in the lymphoid organs, possibly by increased ROS generation. There are several instances of autophagy and apoptosis taking place either simultaneously or sequentially due to oxidative stress. Since arsenic is a potent environmental stress factor, exposure to arsenic led to a dose-dependent increase in both autophagy and apoptosis in the thymus and spleen, and cell death could therefore possibly be induced by autophagy. Therefore, exposure to arsenic leads to serious effects on the immune physiology in mice, which may further have dire consequences on the health of exposed animals.


Assuntos
Arsênico/farmacologia , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arsenitos/farmacologia , Relação CD4-CD8 , Inflamação/induzido quimicamente , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
16.
Biomed Pharmacother ; 121: 109591, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733576

RESUMO

The present study was done to evaluate the prebiotic effect of Lycium barbarum polysaccharide (LBP), its effect on murine fecal microbiota composition and innate immune response. Results showed that LBP supports the growth of selective probiotic bacteria with a maximum of 8.23 (log10 cfu/mL) and 6.62 (log10 cfu/mL) for Lactobacillus acidophilus and Bifidobacterium longum respectively. In vivo studies revealed that the administrations of LBP to mice resulted in an increase in the abundance of the phyla Proteobacteria and Firmicutes, while reducing the ratio of the phylum Bacteroidetes. At the genus level, the administration of LBP stimulated the emergence of some potential probiotic genera (Akkermansia, Lactobacillus, and Prevotellaceae). The concentrations of TGF-ß and IL-6 in serum and sIgA in the colon content were enriched significantly after LBP administrations in mice. The thymus index and spleen index of mice treated with LBP displayed significant difference compared to the control group (P < 0.05). These findings suggest that LBP is a good source as a potential prebiotic and can enhance the intestinal microbiota and boost beneficial bacteria levels, modulate innate immune response.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Prebióticos/administração & dosagem , Animais , Citocinas/imunologia , Citocinas/metabolismo , Camundongos , Distribuição Aleatória , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Timo/efeitos dos fármacos , Timo/imunologia , Timo/metabolismo
17.
BMC Complement Altern Med ; 19(1): 322, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752816

RESUMO

BACKGROUND: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. METHODS: For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. RESULTS: PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. CONCLUSIONS: Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.


Assuntos
Adjuvantes Imunológicos/farmacologia , Ciclofosfamida/efeitos adversos , Extratos Vegetais/farmacologia , Platycodon , Baço , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Tolerância Imunológica/efeitos dos fármacos , Imunossupressão , Imunossupressores/efeitos adversos , Ratos , Baço/citologia , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
18.
Int Immunopharmacol ; 76: 105913, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31627170

RESUMO

Radiation exposure poses a significant threat to public health, which can lead to acute hematopoietic system and intestinal system injuries due to their higher radiation sensitivity. Hence, antioxidants and thiol-reducing agents could have a potential protective effect against this complication. The dithiol compound 1,4-dithiothreitol (DTT) has been used in biochemistry, peptide/protein chemistry and clinical medicine. However, the effect of DTT on ionizing radiation (IR)-induced hematopoietic injury and intestinal injury are unknown. The current investigation was designed to evaluate the effect of DTT as a safe and clinically applicable thiol-radioprotector in irradiated mice. DTT treatment improved the survival of irradiated mice and ameliorated whole body irradiation (WBI)-induced hematopoietic injury by attenuating myelosuppression and myeloid skewing, increasing self-renewal and differentiation of hematopoietic progenitor cells/hematopoietic stem cells (HPCs/HSCs). In addition, DTT treatment protected mice from abdominal irradiation (ABI)-induced changes in crypt-villus structures and function. Furthermore, treatment with DTT significantly enhanced the ABI-induced reduction in Olfm4 positive cells and offspring cells of Lgr5+ stem cells, including lysozyme+ Paneth cells and Ki67+ cells. Moreover, IR-induced DNA strand break damage, and the expression of proapoptotic-p53, Bax, Bak protein and antiapoptotic-Bcl-2 protein were reversed in DTT treated mice, and DTT also promoted small intestine repair after radiation exposure via the p53 intrinsic apoptotic pathway. In general, these results demonstrated the potential of DTT for protection against hematopoietic injury and intestinal injury after radiation exposure, suggesting DTT as a novel effective agent for radioprotection.


Assuntos
Síndrome Aguda da Radiação/tratamento farmacológico , Ditiotreitol/uso terapêutico , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Síndrome Aguda da Radiação/metabolismo , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ditiotreitol/farmacologia , Raios gama/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos da radiação , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Masculino , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Lesões Experimentais por Radiação/metabolismo , Protetores contra Radiação/farmacologia , Baço/efeitos dos fármacos , Baço/efeitos da radiação , Timo/efeitos dos fármacos , Timo/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo , Irradiação Corporal Total
19.
Vet Res ; 50(1): 83, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639045

RESUMO

The thymus is a primary lymphoid organ and plays a critical role in the immune response against infectious agents. Baicalin is a naturally derived flavonoid famous for its pharmacological properties, but the preventive effects of baicalin against immune impairment remain unclear. We examined this effect in the context of Mycoplasma gallisepticum (MG) infection-induced structural damage in the chicken thymus. Histopathological examination showed that the compact arrangement of cells in the thymus was lost in the MG-infected group. Inflammatory cell infiltration and nuclear debris accumulated, and the boundary between the cortex and medulla was not clearly visible. The mRNA and protein expression of apoptosis-related genes were significantly increased in the MG-infected group compared to the control group and the baicalin group. The number of positively stained nuclei in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay were increased in the MG-infected group. In addition, electron microscopic examination showed chromatin condensation, mitochondrial swelling and apoptotic vesicles in the MG-infected group. However, baicalin treatment significantly alleviated the oxidative stress and apoptosis induced by MG infection. Importantly, the abnormal morphology was partially ameliorated by baicalin treatment. Compared to the MG-infected group, the baicalin-treated group showed significantly reduced expression of apoptosis-related genes at both the mRNA and protein levels. Meanwhile, the nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway and downstream genes were significantly upregulated by baicalin to counteract MG-induced oxidative stress and apoptosis in the thymocytes of chickens. In summary, these findings suggest that baicalin treatment efficiently attenuated oxidative stress and apoptosis by activating the Nrf2 signalling pathway and could protect the thymus from MG infection-mediated structural and functional damage.


Assuntos
Galinhas , Flavonoides/farmacologia , Mycoplasma gallisepticum/fisiologia , Doenças das Aves Domésticas/tratamento farmacológico , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo/efeitos dos fármacos , Doenças das Aves Domésticas/microbiologia , Transdução de Sinais/genética , Timo/microbiologia , Timo/patologia , Regulação para Cima
20.
Bull Exp Biol Med ; 167(5): 624-627, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31606806

RESUMO

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 µg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Estresse Psicológico/fisiopatologia , Timo/efeitos dos fármacos , Glândulas Suprarrenais/fisiopatologia , Animais , Imobilização/métodos , Injeções Intraperitoneais , Masculino , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/imunologia , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/fisiopatologia , Estresse Psicológico/imunologia , Estresse Psicológico/prevenção & controle , Timo/fisiopatologia
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