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1.
Adv Exp Med Biol ; 1155: 381-390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468416

RESUMO

Taurine (2-aminoethanesulfonic acid) has positive effects on the formation of immune systems. In this study, we evaluated the effects of taurine on the development of T lymphocyte subpopulations in thymus of immunosuppresive mice. The immunosuppressed mice model was established by intraperitoneal injection of dexamethasone (Dex) for 7 days. Mice (male, Kunming strain) were randomly divided into three groups, the normal control group (Cont.), the Dex-induced immunosuppressive model group (Dex + PBS), and the taurine intervention group (Dex + TAU). Taurine was administered at a dose of 200 mg/kg for 30 days or until euthanasia. Total cell numbers in the thymi of mice were evaluated by cell count, and the flow cytometry was used to determine the proportion of different cell subsets. Our results showed that the size and weight of thymi of Dex + PBS group were significantly smaller than those of Cont. group, and taurine administration efficiently increased the thymus index. Taurine also significantly increased the number of CD4- CD8- double negative (DN), CD4+ CD8+ double positive (DP), CD4+ single positive (CD4+) and CD8+ SP (CD8+) cells compared with the Dex + PBS group, but did not affect the CD4+/CD8+ cell ratio in thymus of Dex-induced immunoseppressive mice. Our results suggested that taurine has a positive effect on thymus differentiation in Dex-induced immunosuppressive mice.


Assuntos
Diferenciação Celular , Imunossupressão , Subpopulações de Linfócitos T/efeitos dos fármacos , Taurina/farmacologia , Timo/efeitos dos fármacos , Animais , Relação CD4-CD8 , Dexametasona , Citometria de Fluxo , Masculino , Camundongos , Distribuição Aleatória , Subpopulações de Linfócitos T/citologia
2.
Georgian Med News ; (291): 112-117, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31418742

RESUMO

The scientific interest in the influence of xenobiotics on the human body is due to the fact that immune organs are characterized by a pronounced response to the influence of endogenous and exogenous factors. Recently, the immunological impairment, as a manifestation of reactions to ecopathogenic conditions, suggests a major pathogenesis role in the development of cardiovascular, neuropsychiatric diseases, as well as diffuse diseases of connective tissue. Objectives - experiment was designed to elucidate the organometric changes in thymus of male rats due to impact of propylene glycol. 40 WAG matured male rats were divided randomly into two groups. The first group served as a control and constituted 8 animals. The second group of 32 rats, 8 rodents in each, were treated via gavage by aqueous solutions of propylene glycol in doze 1/10 LD50 in conversion to 26,38 g/kg during 7, 15, 30, 45 days. All animals were sacrificed on the term defined by experimental design. Thymus specimens were dissected out, and linear dimensions (length, width, height) using digital caliper were measured, along with mass and volume of the thymus. Limits of the thymus morphometric indices' variability in intact and experimental groups were calculated. The research indicates that exposure to propylene glycol caused marked organometric changes in rats' thymus. However, more pronounced changes were observed on 7th and 30th days. Were established the following limits of variability indices oscillations: IndHL of the experimental group thymus ranged from min=12.57 to max=47.54, the mean value was from 24.67 to 28.02; IndHW of the experimental group thymus ranged from min=11.96 to max=88.73, the mean value was from 36.78 to 41.41; IndT of the experimental group ranged from min = 38.17 to max=141.3, the mean value was from 71.1 to 86.52. The study of the morphometric parameters of the thymus in the experimental group of rats has established a significant reduction of all parameters and their deviation from the parameters of the control group, that shows active reaction of thymus on induced xenobiotic.


Assuntos
Propilenoglicóis/farmacologia , Timo/efeitos dos fármacos , Animais , Masculino , Propilenoglicóis/administração & dosagem , Distribuição Aleatória , Ratos , Xenobióticos/administração & dosagem , Xenobióticos/farmacologia
3.
BMC Complement Altern Med ; 19(1): 126, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185967

RESUMO

BACKGROUND: Gut microbiota plays a crucial role in the treatment of gastrointestinal (GI) diseases such as chemotherapy-induced diarrhea (CID). Shenzhu Capsule (SZC) is a Chinese herbal formula, which is composed of Renshen (rhizomes of Panax ginseng C. A. Mey.) and Baizhu (rhizomes of Atractylodes macrocephala Koidz.). Many Chinese traditional anti-diarrheal formulae that contain Renshen and Baizhu are capable of effectively alleviating CID. However, the efficacy in vivo and potential mechanism of SZC (the form of compatibility of Renshen and Baizhu) in the treatment of CID had not been elucidated. Here, this study aimed to investigate whether SZC exhibited the anti-diarrheal activity, and whether gut microbiota was involved in the therapeutic effect of SZC on CID. METHODS: High performance liquid chromatography (HPLC), gas chromatography-mass spectrometer (GC-MS) and infrared spectroscopy (IR) analyses were used to characterize the extracted components in SZC. The mice were orally administrated with SZC in a preventive mode on the first 2 days of this experiment, and then intraperitoneally injected with 5-FU (40 mg/kg/d) for 6 days. SZC treatment lasted until the 3rd day after the end of 5-FU chemotherapy. We investigated the effects of SZC on body weights, diarrhea, thymus/spleen indexes, colonic tissues, and gut microbiota. Colonic histology was examined by hematoxylin-eosin (HE) staining. 16S rDNA Amplicon Sequencing was used to analyze the gut microbial structure from fecal samples. RESULTS: SZC significantly increased the body weights and thymus/spleen indexes, alleviated diarrhea, and reversed histopathological changes of colons. In addition, gut microbiota analysis revealed that the overall structure of gut microbiota in CID mice was disturbed, but reversed to the normal state after SZC treatment. At genus level, SZC significantly inhibited the growth of some potential pathogens associated with diarrhea, such as Clostridiumm, Bacteroides, Parabacteroides, Alloprevotella, Acinetobacter and Pseudomonas. CONCLUSIONS: In our study, these data illustrated that SZC inhibited the growth of many potential pathogens during the alleviation of CID. Gut microbial modulation was associated with the anti-diarrheal activity of SZC.


Assuntos
Atractylodes/química , Diarreia/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Panax/química , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Diarreia/induzido quimicamente , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Fluoruracila/efeitos adversos , Masculino , Camundongos , Fitoterapia , Distribuição Aleatória , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
4.
Biomed Res Int ; 2019: 1602895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179315

RESUMO

The aim was to investigate the effect of dichloroacetate (DCA) on thymus weight, Hassall's corpuscle number (HCs), and NKCC1 RNA expression in Wistar rats aged 4-5 weeks. They were investigated in the controls and DCA-treated gonad-intact and castrated males and females. The treatment lasted 4 weeks with DCA 200 mg/kg/day. At the end of the experiment, rat thymus was weighted, and its lobe was taken for the expression of NKCC1 RNA determined by the PCR method and of Hassall's corpuscles by immunohistochemistry. DCA caused a thymus weight decrease in DCA-treated gonad-intact rats of both genders as compared with their controls (p < 0.05), and no such impact was found in castrated DCA-treated males and females. DCA caused an increase of the HCs in gonad-intact males (p < 0.05), and no such increase in the DCA-treated gonad-intact females was found. There was gender-related difference in the HCs when comparing DCA-treated gonad-intact males and females: males showed significantly higher HCs (p < 0.05); no gender-related differences were found in the castrated DCA-treated groups. The Slc12a2 gene RNA expression level was found to be significantly decreased only in gonad-intact and in castrated DCA-treated males. The authors discuss the gender-related DCA effects on the thymus.


Assuntos
Ácido Dicloroacético/farmacologia , Células Epiteliais/efeitos dos fármacos , RNA/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Timo/efeitos dos fármacos , Animais , Castração , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Imuno-Histoquímica , Masculino , Orquiectomia , Ratos , Ratos Wistar , Timo/patologia
5.
Biochemistry (Mosc) ; 84(6): 617-626, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31238861

RESUMO

D-Galactose (D-Gal) promotes accumulation of reactive oxygen species and formation of advanced glycation end-products, ultimately resulting in oxidative stress. D-Gal has been widely used to induce accelerated aging in anti-aging medical research. Although thymic epithelial cells are particularly sensitive to oxidative stress, there are few reports on the thymus changes accompanying D-Gal-induced aging in mice. To study the effect of D-Gal on rodent thymus, we investigated the degree of thymus atrophy and changes in the atrophy relative index in C57BL/6J mice following subcutaneous injection of D-Gal at different doses (200, 500, 1000 mg/kg per day) for 60 days. Compared with the vehicle-treated (0.9% saline) and young controls, D-Gal at doses of 500 and 1000 mg/kg per day led to a significant thymic atrophy; the latter dose caused atrophy similar to that observed in naturally aged (18-20-month-old) mice. Mice treated with high-dose D-Gal exhibited greater immunosenescence, defective central immune tolerance, increased levels of activated splenic immune cell, and chronic low-grade inflammation, i.e., outcomes similar to those observed in natural aging in mice. Taken together, our results indicate that mice treated with high-dose D-Gal may be a valid model for studying induced thymic atrophy and effects of aging on the immune system.


Assuntos
Envelhecimento/efeitos dos fármacos , Galactose/administração & dosagem , Tolerância Imunológica , Animais , Relação Dose-Resposta a Droga , Feminino , Galactose/farmacologia , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/patologia
6.
Int J Nanomedicine ; 14: 2995-3013, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118618

RESUMO

Background: Recent years, there occurs heavy haze pollution in northern China during wintertime. The potential influence of airborne particulate matter (PM) on human health attracts great concern. The fuel-derived PM in the inhalable size range is dominated by aggregates of nanoparticles of Carbon black (CB). However, there are still lack of evidences especially regarding long-term exposure to explain the chronic effects of nanoscaled CB and the relative mechanism. Purpose: The objective of this study was to identify the potential mechanism of chronic effects of nanoscale CB. The systemic toxicity, immune suppression or activity and local toxicity were evaluated. Methods: 32 rats were divided into 2 groups: 30 mg/m3 CB exposure (nose only, 90 d, 6h/d) and control (clean air). Half of rats were scarified after exposure and another half of rats recovered for 14 days. Eight rats in each group were executed the lung function tests using a ventilated bias flow whole body plethysmograph (WBP). SDS-PAGE protocol was used to detect the deposition and retention of CB in lung of rats. HE staining was used to observe the changes of histopathology. Cell apoptosis was examined by TUNEL assay or flow cytometry. The levels of IL-6, IL-8, IL-17 and TNF-α in serum and lung tissue were evaluated with commercially available ELISA kit. The peripheral blood cell counts were detected by Auto 5-diff hematology analyzer. Results: The lung burden of CB was 16 mg in lung of rats after a 90-day exposure by MPPD. Fourteen percentages of the amount of CB accumulated at the end of the exposure period was cleared from the lung during the 14 dys recovery period. The lung function was significantly decreased and could not recover after a short time recovery. The fibroblasts and granuloma formation were found in lung. The levels of apoptosis and DNA damages were significantly increased in lung cells after CB inhalation. The cytokines levels in lung but not in serum were significantly increased in CB exposure group. The cell counts of WBC, monocytes and neutrophils had 1.72, 3.13, and 2.73-fold increases after CB exposure, respectively. The percentages of CD4+ lymphocytes and the rates of CD4+/CD8+ were statistically increased after CB exposure. The stimulation indexes of the peripheral blood lymphocytes were significantly decreased after CB exposure. In the CB exposure group, the disrupted histomorphology of thymus and spleen were found as well as the early apoptotic thymocytes had a 2.36-fold increase. Conclusion: CB induced the localized or direct toxicity and systemic immune toxicity. The direct and systemic immune responses had a combined effect on the lung damages caused by CB.


Assuntos
Pulmão/efeitos dos fármacos , Pulmão/imunologia , Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Fuligem/administração & dosagem , Fuligem/toxicidade , Administração por Inalação , Animais , Apoptose/efeitos dos fármacos , Contagem de Células Sanguíneas , China , Citocinas/metabolismo , Inflamação/patologia , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Material Particulado/toxicidade , Ratos Sprague-Dawley , Testes de Função Respiratória , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/patologia
7.
Wiad Lek ; 72(3): 362-367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050981

RESUMO

OBJECTIVE: Introduction: Cyclophosphamide has wide spectrum usage as first-line drug in cancer chemotherapy that is why a detailed study of its effect on individual cell populations is of great interest for science and practice. The interaction of the nervous, immune and endocrine systems plays essential role in the homeostasis maintaining. The aim: This study aimed to investigate the ultramicroscopic changes that occur in the parathyroid glands and thymus of male rats after cyclophosphamide administration. PATIENTS AND METHODS: Materials and methods: Twenty-four WAG matured male rats were divided randomly into two groups. The first group served as control and was provided 0.9% soluble sodium chloride. The second group received cyclophosphamide in a dosage 200 mg/kg of body weight of animal by intramuscular single injection. All animals were sacrificed on the 7th and 30th day after injection. Parathyroid gland and thymus specimens were dissected out and processed for electron microscopy. RESULTS: Results: The results showed that cyclophosphamide exposure caused marked ultramicroscopic changes in rats parathyroid glands and thymus. On the 7th day after immunosuppression, the nuclei of parathyrocytes have deep wavy invaginations, amount of the organelles that participate in the protein synthesis is reduced to a minimum in the cytoplasm of the chief cells. Characteristic feature is the appearance of numerous plasma cells and active macrophages in thymus. There is a tendency to normalization of the parathyroid structure on the 30th day after administration of cyclophosphamide and reduction of mitotic activity of lymphocytes in thymus, which points to the development of involution process. CONCLUSION: Conclusions: This data can be successfully extrapolated from experimental animals to humans.


Assuntos
Ciclofosfamida/administração & dosagem , Glândulas Paratireoides , Timo , Animais , Humanos , Imunossupressão , Masculino , Microscopia Eletrônica , Glândulas Paratireoides/efeitos dos fármacos , Ratos , Timo/efeitos dos fármacos
8.
Int Immunopharmacol ; 72: 98-111, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30974284

RESUMO

Ginsenoside Rg3 (Rg3), which comprises Panax ginseng, is commonly used to improve the immunocompetence of cancer patients undergoing chemotherapy. This study was designed to elucidate the immunoenhancement effects of Rg3 in immunosuppressed mice induced by cyclophosphamide (CTX) treatment. Balb/c mice were administered Rg3 intragastrically once daily for 19 consecutive days and were intraperitoneally administered CTX (80 mg/kg) on days 15-19. Weight and immune organ indices were recorded. Hematological tests and cytokines were assessed using ELISA. We measured the activity of LDH and ACP, performed pathological and immunohistochemical staining of immune organs, and evaluated cytokines and transcription factors using RT-PCR. Immunosuppressed mice showed weight loss, decreased thymus and spleen indices and severe pathological damage. CTX attenuated macrophage phagocytosis by decreasing activity of LDH and ACP and decreased the release of related immune factors, IgG, IL-2 and G-CSF. Subsequently, we observed T lymphocyte expression on the surface of the thymus and spleen, which inhibited T cell activity. Further mechanistic analysis showed that CTX decreased the expression of T-bet and IFN-γ and increased the expression of GATA-3 and IL-4 in the thymus and spleen, which affected the Th1/Th2 balance. However, Rg3 treatment reversed CTX-induced immunosuppression. In summary, all the results suggest that Rg3 has protective effects on CTX-induced immunosuppression, which could be partially related to macrophages, T cells and Th1/Th2 balance. Although deeper studies of its mechanism are needed, these findings support the hypothesis that Rg3 can improve the reduced immunocompetence after CTX injury.


Assuntos
Ciclofosfamida/efeitos adversos , Ginsenosídeos/farmacologia , Fatores Imunológicos/farmacologia , Imunossupressão , Animais , Fator Estimulador de Colônias de Granulócitos/sangue , Imunoglobulina G/sangue , Fatores Imunológicos/efeitos adversos , Interleucina-2/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Timo/patologia
9.
Biomed Pharmacother ; 112: 108709, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970514

RESUMO

OBJECTIVE: Poria cocos polysaccharide (PCP) is the major active ingredients of P. cocos and possesses various pharmacological effects, including anti-oxidative and anti-apoptosis effects and activity against cancer. This study investigated the immunomodulatory mechanism by which PCP acts on RAW 264.7 macrophages and LLC tumors in mice. METHODS: The concentrations of nitric oxide, and Th1, Th2, and Th17 cytokines were examined by Griess reaction and using a bead-based cytokine assessment kit. qRT-PCR and western blotting were used to investigate relevant signaling molecule expression. RESULTS: Levels of nitric oxide, IL-2, IL-6, IL-17 A, TNF, and IFN-γ were increased by PCP while levels of IL-4 and IL-10 were unaffected. The addition of TAK-242 (TLR4 inhibitor) or assessment in C57BL/10ScNJ (TLR4-deficient) mice markedly reduced this effect. In C57BL/10 J (TLR4+/+wild-type) mice, the indices of organ immune activity were all elevated, and oral PCP delivery resulted in a significant reduction in tumor volume over a 25 day period. Relative to controls, TLR4, MyD88, TRAF-6, p-NF-κB and p-c-JUN expression significantly increased, while TRAM expression did not change. Nevertheless, there was no PCP-dependent activation of MyD88, TRAF-6, TRAM, p-NF-κB or p-c-JUN in TLR4-deficient mice. CONCLUSION: These results support the concept that PCP may exhibit immunomodulatory activity through TLR4/TRAF6/NF-κB signaling both in vitro and in vivo.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , NF-kappa B/metabolismo , Polissacarídeos/uso terapêutico , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/metabolismo , Wolfiporia/química , Animais , Antineoplásicos/isolamento & purificação , Carcinoma Pulmonar de Lewis/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Feminino , Fatores Imunológicos/isolamento & purificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
10.
Int J Biol Macromol ; 133: 1107-1114, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31022488

RESUMO

The effects of alfalfa polysaccharides (APS) on immunomodulatory and antioxidant functions, as well as intestinal morphology were investigated in vivo in this study. Sixty-four mice were randomly divided into four groups and administered 0, 200, 400 or 800 mg/kg/d body weight APS via gavage for 28 days. The blood parameters and metabolites, viscera indices, antioxidant enzyme activities and intestinal morphology were measured. The results showed that the oral administration of APS improved the immune functions of mice, significantly enhanced the white blood cells and lymphocyte counts, and led to improvements in spleen and thymus indices. APS exhibited significant antioxidant activity by enhancing total antioxidant capacity, superoxide dismutase and glutathione peroxidase activities in heart, kidney and liver, and decreasing the malondialdehyde levels of heart and liver. Moreover, administration of APS potently enhanced the small intestinal villous height and the villus-to-crypt ratio, and decreased the crypt depth of duodenum in mice. Therefore, we can conclude that APS possesses pronounced immunomodulatory activities, and plays an important role in the prevention of oxidative stresses and in the improvement of intestinal morphology in the immunological system in vivo. APS thus shows potential for the development as an effective natural immunomodulatory and antioxidant agent.


Assuntos
Antioxidantes/farmacologia , Fatores Imunológicos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Medicago sativa/química , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Feminino , Fatores Imunológicos/química , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Polissacarídeos/química , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
11.
Ecotoxicol Environ Saf ; 176: 146-152, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925331

RESUMO

Ammonia (NH3) is one of major air pollutants in intensive poultry houses, affecting chicken health. Circular RNA (circRNA) is a novel type of RNA that can regulate gene expression and be associated with various biological activities. However, the changes of circRNA caused by excess NH3 in chickens have not been investigated. We found differentially expressed genes and morphological changes in the thymuses of chickens exposed to NH3 on day 42. We used a combination of RNA deep sequencing, qRT-PCR, and bioinformatic analysis to explore regulatory mechanism of circRNA and mRNA. Transcriptional profiling results showed that 5 circRNA genes and 100 mRNA genes were significantly dyregulated by high NH3. The results from GO items showed that immune response and the regulation of cytokine production were involved in the mechanisms of chickens exposed to NH3. Co-expression analysis found that circRNA-mRNA network was correlated with oxidative stress and inflammation. NH3 exposure decreased mRNA expression of antioxidant-related genes (GPx and GST4) and increased the mRNA expression of inflammation-related genes (IL-1ß, IL-6, IL-8, and iNOS) in chicken thymuses. Histopathologic analysis demonstrated that NH3 caused inflammatory injury in chicken thymuses. In conclusion, the co-expression of circRNA and mRNA took part in chicken thymus inflammatory injury caused by NH3. Our study further enriches the mechanism of NH3 toxicity on chickens, which may be valuable for human and animal health protection.


Assuntos
Amônia/toxicidade , Galinhas , Expressão Gênica/efeitos dos fármacos , RNA/genética , Timo/efeitos dos fármacos , Animais , Inflamação/genética , Exposição por Inalação/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Timo/imunologia , Timo/patologia
12.
Regul Toxicol Pharmacol ; 104: 50-55, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30826316

RESUMO

Di (2-ethylhexyl) adipate (DEHA) is a potential plasticizer alternative for di-2-ethylhexyl phthalate (DEHP). Toxicity of DEHA has been studied mostly via oral exposure but not assessed after repeated intravenous exposure. The present study shows the toxicity effects after intravenous administration for 28 consecutive days and the reversibility of the effects following a 14-day recovery period. The study was conducted under GLP conditions. Four groups of rats (15/sex/group) each received either vehicle or DEHA in vehicle (100, 200, or 450 mg/kg/day). Criteria for evaluation included clinical observations, body weight, food consumption, clinical pathology (hematology, serum chemistry, coagulation, urinalyses), gross (necropsy) evaluation, organ weight and histopathological evaluation. There were no DEHA-related changes in all the endpoints evaluated at 100 or 200 mg/kg/day. There were no test article-related changes in clinical pathology or gross necropsy observation at 450 mg/kg/day. At the high-dose, DEHA-related findings included clinical observations, decreased body weight gain and food consumption, increased liver weight in females associated with minimal hepatocellular hypertrophy, and decreased thymus weight in males and females without histopathology findings. All these findings were completely reversible within a 14-day recovery period. Therefore, the 200 mg/kg/day dose is considered to be the No-Observed-Effect Level (NOEL).


Assuntos
Adipatos/administração & dosagem , Adipatos/toxicidade , Peso Corporal/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Fígado/efeitos dos fármacos , Timo/efeitos dos fármacos , Administração Intravenosa , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
13.
J Sci Food Agric ; 99(8): 4019-4028, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30729524

RESUMO

BACKGROUND: The intestinal microbiota has a wide variety of functions in the host. A positive effect of plant extract on intestinal microbiota in animals has been reported. However, the effect of orange essential oil and its components limonene, linalool and citral on intestinal microflora in mice has seldom been reported. The effects of intragastric administration of orange essential oil and limonene, linalool and citral on intestinal microflora and biochemical indexes in mice were studied. RESULTS: The effect of essential oil, linalool and citral on immune organ index (spleen and thymus index), IgM and IL-2 was not significant (P > 0.05). A significant increase (P < 0.05) of H+ K+ -ATPase activity, IgA, IgG, and IL-2 in the limonene group was observed when compared with the control group. Orange essential oil, limonene, linalool and citral could significantly reduce the content of short-chain fatty acids in the cecum and colon of mice. Principal coordinates analysis showed that intestinal bacterial structure of limonene group cecum and colon was apparently separated from other groups. The relative abundance of Lactobacillus in cecum and colon in essential oil, limonene, linalool and citral groups was higher than that in the control group. CONCLUSIONS: Orange essential oil and limonene, linalool and citral could affect the intestinal microflora of mice, and enhance the relative abundance of Lactobacillus. The intestinal bacterial structure of cecum and colon in the limonene group was quite different from other groups. This indicated a more obvious effect of limonene on intestinal bacteria, also resulting in significant changes in blood immune index and short-chain fatty acids in mice. © 2019 Society of Chemical Industry.


Assuntos
Citrus sinensis/química , Microbioma Gastrointestinal/efeitos dos fármacos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Intestinos/imunologia , Intestinos/microbiologia , Masculino , Camundongos , Óleos Voláteis/química , Filogenia , Extratos Vegetais/química , Baço/efeitos dos fármacos , Baço/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
14.
Toxicol Lett ; 304: 30-38, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30605750

RESUMO

Clinical study showed that smoking during pregnancy deceased the thymus size in newborns. However, the long-term effect remains unclear. This study was aimed to observe the effects of prenatal nicotine exposure (PNE) on the development of thymus and the T-lymphocyte subpopulation in mice offspring from the neonatal to adulthood. Both the thymus weight and cytometry data indicated that PNE caused persistent thymic hypoplasia in male offspring from neonatal to adult period and transient changes in female offspring from neonatal to prepuberal period. Flow cytometry analysis disclosed a permanent decreased proportion and number of mature CD4 single-positive (SP) T cells in thymus of both sex. In addition, the PNE male offspring showed a more serious thymus atrophy in the ovalbumin (OVA)-sensitized model. Moreover, increased autophagic vacuole and elevated mRNA expression of Beclin 1 were noted in PNE fetal thymus. In conclusion, PNE offspring showed thymus atrophy and CD 4 SP T cell reduction at different life stages. Mechanically, PNE induced excessive autophagy in fetal thymocytes might be involved in these changes. All the results provided evidence for elucidating the PNE-induced programmed immune diseases.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Doenças do Sistema Imunitário/induzido quimicamente , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Timócitos/efeitos dos fármacos , Timo/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Feminino , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Doenças do Sistema Imunitário/patologia , Masculino , Exposição Materna , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Fenótipo , Gravidez , Timócitos/imunologia , Timócitos/metabolismo , Timócitos/patologia , Timo/imunologia , Timo/metabolismo , Timo/patologia
15.
Food Chem Toxicol ; 125: 62-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597219

RESUMO

Effects of Maillard reaction products derived from 1 to 3 kDa soybean peptides (MRPF3) on aging ICR mice were investigated. Seven animal groups were established for 5 weeks, including one normal group and six D-galactose (1000 mg kg-1/day) treated groups. Aging control was D-galactose + saline solution, and positive controls were D-galactose + ascorbic acid (Vc) (400 mg kg-1/day) and oligofructose (400 mg kg-1/day), respectively, while the test groups are D-galactose + high (800 mg kg-1/day), medium (400 mg kg-1/day) and low (200 mg kg-1/day) doses of MRPF3. Compared with the aging controls, food intake, body weights and organ indexes returned to normal after feeding with MRPF3, and the color of feces as well as the fluorescence intensity of urine increased. The content of malondialdehyde (MDA) in the liver significantly decreased with the intake of MRPF3, and the activities of SOD and GSH-Px and the total antioxidant capacity of serum significantly increased. The abundance ratio of Bacteroidetes and Firmicutes significantly decreased in MRPF3 groups, and the abundance of Lactobacillus significantly increased, while potentially pathogenic bacteria such as Porphyromonadaceae significantly decreased. Our results showed that MRPF3 might offer a potent retardation potential for aging.


Assuntos
Envelhecimento/metabolismo , Reação de Maillard , Proteínas de Plantas/farmacologia , Soja/química , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteínas de Plantas/química , Baço/efeitos dos fármacos , Baço/metabolismo , Superóxido Dismutase/metabolismo , Timo/efeitos dos fármacos , Timo/metabolismo
16.
J Agric Food Chem ; 67(5): 1402-1408, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30629411

RESUMO

Ginsenoside compound K (CK) is not a ginsenoside that naturally exists in Panax ginseng Meyer. However, CK is a major metabolite of ginsenoside Rb1, Rb2, or Rc in the intestine under the effects of bacteria. In this study, we first investigated the effects of CK on myelosuppression in mice induced by cyclophosphamide (CTX). The respective quantities of white blood cells, blood platelets, and bone marrow nucleated cells (BMNCs) were determined to be 8.54 ± 0.91 (109/L), 850.90 ± 44.11 (109/L), and 1.45 ± 0.22 (109/L) in the CK-H group by detecting peripheral blood cells and BMNCs. CK-H and CK-L both increased the thymus index by up to 0.62 ± 0.06 (mg/g) and 0.52 ± 0.09 (mg/g), respectively, and significantly increased the yields of colony formation units-granulocyte monocyte and colony formation units-megakaryocytic. According to our study, CK could control apoptosis and promote cells to enter the normal cell cycle by the bcl-2/bax signaling pathway and MEK/ERK signaling pathway. Therefore, the BMNCs could proliferate and differentiate normally after entering the normal cell cycle. So the peripheral blood cells could show a trend of returning to normal. The recovery of peripheral blood cells resulting in the level of cytokines tended to normal. This process may be the mechanisms of CK on myelosuppression. This study provides a reference for ginseng in the treatment of myelosuppression.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Células Mieloides/efeitos dos fármacos , Mielopoese/efeitos dos fármacos , Panax/química , Animais , Apoptose/efeitos dos fármacos , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Ciclo Celular , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Mieloides/citologia , Baço/citologia , Baço/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacos
17.
Biol Trace Elem Res ; 189(1): 209-223, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30094741

RESUMO

The objective of this study is to construct a digital gene expression tag profile to identify genes potentially related to immune response in the ostrich. Exposure to boron leads to an immune response in the ostrich, although the underlying mechanism remains obscure. Thus, a dire need of biological resource in the form of transcriptomic data for ostriches arises to key out genes and to gain insights into the function of boron on the immune response of thymus. For this purpose, RNA-Seq analysis was performed using the Illumina technique to investigate differentially expressed genes in ostrich thymuses treated with different boric acid concentrations (0, 80, and 640 mg/L). Compared with the control group, we identified 309 upregulated and 593 downregulated genes in the 80 mg/L treated sample and 228 upregulated and 1816 downregulated genes in 640 mg/L treated sample, respectively. Trend analysis of these differentially expressed genes uncovers three statistically significant trends. Functional annotation analysis of the differentially expressed genes verifies multiple functions associated with immune response. When ostrich thymuses were treated with boron, expression changes were observed in genes predominantly associated with MAPK and calcium signaling pathways. The results of this study provide all-inclusive information on gene expression at the transcriptional level that further enhances our apprehension for the molecular mechanisms of boron on the ostrich immune system. The calcium and MAPK signaling pathways might play a pivotal role in regulating the immune response of boron-treated ostriches.


Assuntos
Boro/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Timo/efeitos dos fármacos , Timo/imunologia , Timo/metabolismo , Animais , Perfilação da Expressão Gênica , Transdução de Sinais/efeitos dos fármacos , Struthioniformes , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
18.
Fish Shellfish Immunol ; 86: 713-723, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30513382

RESUMO

Besides their obvious role in sex determination and reproduction, oestrogens display a prominent and complex immunomodulatory role across all vertebrates. To date, our knowledge on the oestrogenic immunomodulation in non-mammalian species is, however, scarce. In both teleosts and mammals, the direct immunomodulatory function of oestrogen is underscored by the presence of multiple oestrogen receptor subtypes in the various immune cells. For a better understanding of the regulatory processes, we investigated the oestrogen receptor expression in two major lymphoid organs of European sea bass: the head-kidney and the spleen. All oestrogen receptor subtypes, including nuclear and membrane oestrogen receptors, were present in both immune organs as well as in the isolated leucocytes. The same findings have been previously made for the thymus. To determine the oestrogen responsiveness of the different immune cell populations and to evaluate the importance of non-genomic and genomic pathways, we assessed the kinetics and the concentration dependent effects of 17ß-oestradiol on isolated leucocytes from the head-kidney, the spleen and the thymus in vitro. Given the importance of reactive oxygen species as signalling and defence components in mammalian immune cells, the oxidative burst capacity, the redox status and the viability of both lymphoid and myeloid cells were measured by flow cytometry. The treatment with 17ß-oestradiol specifically modulated these parameters depending on (1) the time kinetic, (2) the concentration of 17ß-oestradiol, (3) the immune cell population (lymphoid and myeloid cells) as well as (4) the lymphoid organs from which they originated. The observed in vitro oestrogenic effects as well the presence of various oestrogen receptor subtypes in the immune cells of sea bass suggest a complex and direct oestrogenic action via multiple interconnected oestrogen-signalling pathways. Additionally, our study suggests that the oestrogenic regulation of the sea bass immune function involves a direct and tissue specific modulation of the immune cell redox biology comprising redox signalling, NADPH-oxidase activity and H2O2-permeability, thus changing oxidative burst capacity and immature T cell fate because oestrogen impacted thymocyte viability. Importantly, immune cells from both primary and secondary lymphoid organs have shown specific in vitro oestrogen-responsiveness. As established in mammals, oestrogen is likely to be specifically and directly involved in immature T cell differentiation and mature immunocompetent cell function in sea bass too.


Assuntos
Bass/imunologia , Estrogênios/imunologia , Leucócitos/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Animais , Diferenciação Celular , Estradiol/farmacologia , Estrogênios/farmacologia , Rim Cefálico/efeitos dos fármacos , Rim Cefálico/imunologia , Peróxido de Hidrogênio/metabolismo , Fatores Imunológicos , Ativação Linfocitária/efeitos dos fármacos , Receptores Estrogênicos/efeitos dos fármacos , Receptores Estrogênicos/genética , Explosão Respiratória , Timo/efeitos dos fármacos , Timo/imunologia
19.
Int Immunopharmacol ; 67: 194-201, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557822

RESUMO

Defect of thymus results in poor posttransplant immune recovery and dysfunction of immune tolerance after allogeneic hematopoietic cell transplants (allo-HCT). Improving thymus regeneration represents a potential strategy to accelerate recovery of T-cell immunity. IL-22 was reported to mediate thymus regeneration after injury. In this study, we found donor T-cell is a major source of IL-22 in allotransplant recipient. Through applying IL-22 knock out (IL-22KO) mice in allo-HCT, we found donor T-cell derived IL-22 promotes thymus regeneration in association with increased level of intra-thymic IL-22. IL-22KO T-cell-transplanted recipients show deficient thymus recovery which is reversed by injection of exogenous IL-22. T-cell derived IL-22 promotes proliferation of thymic epithelial cells (TECs) in vitro. In addition, donor T-cell derived IL-22 increases expression level of Aire in the thymus and decreases skin chronic graft-versus-host disease (GVHD). Furthermore, short-term use of exogenous IL-22 posttransplant accelerates recovery of thymus without increasing severity of acute GVHD. Our data indicate that cross-talk between T-cell and TECs is an important mechanism to mediate reconstitution of T-cell immunity after allo-HCT.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/terapia , Interleucinas/farmacologia , Linfócitos T/metabolismo , Timo/fisiologia , Animais , Linhagem Celular , Sobrevivência Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Regulação da Expressão Gênica , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Timo/efeitos dos fármacos , Doadores de Tecidos , Transplante Homólogo
20.
Pol J Vet Sci ; 21(3): 589-597, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30468342

RESUMO

OBJECTIVE: This study aimed to investigate developmental changes of the thymus and intra- thymic IL-1ß, IL-6 and TNF-α expression in weaned Sprague-Dawley rats induced by lipopolysac- charide. METHODS: Forty healthy weaned rats aged 26 days and weighing 83±4 g were randomly and equally divided into two groups. The lipopolysaccharide group was treated daily with a single injection of lipopolysaccharide for 10 consecutive days, and the saline group was treated with an equal volume of sterilized saline. On the 1st, 4th, 7th and 10th day, histological changes and distribu- tion of IL-1ß-, IL-6- and TNF-α-positive cells were detected in the thymus by hematoxylin-eosin and immunohistochemistry staining, respectively. Subsequently, the expression levels of IL-1ß, IL-6 and TNF-α were evaluated in the thymus by the ELISA method. RESULTS: Thymus weight and index were significantly smaller in lipopolysaccharide-treated rats than in saline-treated rats (p⟨0.05), but no substantial changes were found in the thymus microstructure after lipopolysaccharide induction. Moreover, a large number of IL-1ß-, IL-6- and TNF-α-positive cells were observed with brownish-yellow color and mainly distributed in the thy- mus parenchyma, both integrated optical density and average optical density increased signifi- cantly in lipopolysaccharide-treated rats than those in saline-treated rats. Compared with the saline group, most of the thymic homogenates had higher levels of IL-1ß, IL-6 and TNF-α in the lipopolysaccharide group on different days. CONCLUSION: These findings indicate that the thymus atrophied after lipopolysaccharide induction in weaned Sprague-Dawley rats, and excessive production of intrathymic IL-1ß, IL-6 and TNF-α was probably involved in the atrophic process.


Assuntos
Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Timo/efeitos dos fármacos , Timo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-6/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética
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