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1.
J Biochem Mol Toxicol ; 33(11): e22400, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593355

RESUMO

Inflammatory bowel disease (IBD) is a continual ailment condition which engrosses the entire alimentary canal. The IBD can be primarily distinguished into two forms, ulcerative colitis, and Crohn's disease. The major symptoms of IBD include pustules or abscesses, severe abdominal pain, diarrhea, fistula, and stenosis, which may directly affect the patient's quality of life. A variety of mediators can stimulate the circumstances of IBD, some examples include infections by microbes such as bacteria, perturbation of the immune system and the surrounding environment of the intestines. Severe colitis was stimulated in the experimental animals through administering 4% dextran sulfate sodium (DSS) which is mixed in water ad libitum for 6 days. Eriocitrin (30 mg/kg) was then administered to the experimental animals followed by the induction of severe colitis to evaluate the therapeutic prospective of eriocitrin against the colon inflammation stimulated by DSS. In this study, eriocitrin (30 mg/kg) demonstrated significant (P < .05) attenuation activity against the DSS-stimulated severe colitis in experimental animals. Eriocitrin counteracted all of the clinical deleterious effects induced by DSS, such as body-weight loss, colon shortening, histopathological injury, accretion of infiltrated inflammatory cells at the inflamed region and the secretion of inflammatory cytokines. The results clearly showed that eriocitrin effectively attenuated DSS-induced acute colitis in experimental animals.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/farmacologia , Flavanonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Citrus/química , Colo/efeitos dos fármacos , Colo/patologia , Ciclo-Oxigenase 2/análise , Citocinas/metabolismo , Modelos Animais de Doenças , Flavanonas/administração & dosagem , Inflamação/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Peroxidase/metabolismo , Extratos Vegetais/administração & dosagem , Índice de Gravidade de Doença , Perda de Peso/efeitos dos fármacos
2.
Int J Mol Sci ; 20(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181746

RESUMO

Exposure to ultrafine particles (UFPs) leads to adverse effects on health caused by an unbalanced ratio between UFPs deposition and clearance efficacy. Since air pollution toxicity is first direct to cardiorespiratory system, we compared the acute and sub-acute effects of diesel exhaust particles (DEP) and biomass burning-derived particles (BB) on bronchoalveolar Lavage Fluid (BALf), lung and heart parenchyma. Markers of cytotoxicity, oxidative stress and inflammation were analysed in male BALB/c mice submitted to single and repeated intra-tracheal instillations of 50 µg UFPs. This in-vivo study showed the activation of inflammatory response (COX-2 and MPO) after exposure to UFPs, both in respiratory and cardiovascular systems. Exposure to DEP results also in pro- and anti-oxidant (HO-1, iNOS, Cyp1b1, Hsp70) protein levels increase, although, stress persist only in cardiac tissue under repeated instillations. Statistical correlations suggest that stress marker variation was probably due to soluble components and/or mediators translocation of from first deposition site. This mechanism, appears more important after repeated instillations, since inflammation and oxidative stress endure only in heart. In summary, chemical composition of UFPs influenced the activation of different responses mediated by their components or pro-inflammatory and pro-oxidative molecules, indicating DEP as the most damaging pollutant in the comparison.


Assuntos
Exposição por Inalação/efeitos adversos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Animais , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Ciclo-Oxigenase 2/análise , Citocromo P-450 CYP1B1/análise , Proteínas de Choque Térmico HSP70/análise , Heme Oxigenase-1/análise , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/análise
3.
Acta Cir Bras ; 34(4): e201900402, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31038582

RESUMO

PURPOSE: To evaluate the effect of amniotic fluid in liver preservation in organ transplantation, and compare it with standard preservation solutions. METHODS: The groups consisted of Group 1: Ringer Lactate (RL) group, Group 2: HTK group, Group 3: UW group, Group 4: AF group. The livers of rats from Group 1, 2, 3, and 4 were perfused and placed into falcon tubes containing RL, HTK, UW, and AF solutions at +4 °C, respectively. The tubes were stored for 12 hours in the refrigerator at +4°C. Tissue samples were taken at the 6th and 12th hours for histopathological examinations of the perfused livers, and storage solutions for biochemical analyzes at 6th and 12th hours. RESULTS: AF was shown to maintain organ viability by reducing the number of cells undergoing apoptosis. Histopathological changes such as sinusoidal dilatation, hydropic degeneration, and focal necrosis were found to be similar to the groups in which the standard organ preservation solutions were used. Additionally, the results of INOS, IL-10, and TNF-α,which were evaluated immunohistochemically, have been shown to be similar to the UW and HTK groups. CONCLUSIONS: AF provided conservation similar to UW and HTK in the 12-hour liver SCS process. The fact that apoptosis values are comparable to standard preservation solutions supports the success of AF in the cold storage of the liver.


Assuntos
Líquido Amniótico , Criopreservação/métodos , Fígado , Soluções para Preservação de Órgãos/farmacologia , Animais , Glucose/farmacologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Interleucina-10/análise , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Manitol/farmacologia , Óxido Nítrico Sintase Tipo II/análise , Preservação de Órgãos/métodos , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Traumatismo por Reperfusão/prevenção & controle , Reprodutibilidade dos Testes , Solução de Ringer/farmacologia , Fatores de Tempo , Sobrevivência de Tecidos , Fator de Necrose Tumoral alfa/análise
4.
Biomed Chromatogr ; 33(6): e4500, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30697775

RESUMO

Traditional herbal medicine consists of multiple components. There are interactions among the components, which affect both potency and toxicity. The preparation of herbal medicines can be a cause of interactions between multicomponents in herbs. To demonstrate the differences in multiherb interactions based on the preparation methods, the changes in the active components in the different preparations of Socheongryong-tang (SCRT) were evaluated using metabolomics profiling. We performed multicomponent profiling of the decoction of SCRT (SCRTD) and individual herb mixture (SCRTM) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Active compounds from SCRTD and SCRTM were identified using multivariate analysis, and the activities between the two groups were compared. We also evaluated the anti-inflammatory effect of SCRT through investigating the protein expression of iNOS and COX-2 in lipopolysaccharide-induced macrophage RAW 264.7 cells in both groups. From the multivariate analysis, 53 active compounds that have different intensities between SCRTD and SCRTM were identified. The intensities of those components, such as ephedrines, glycyrrhizic acid, 6-gingerol and (2E,4E,8Z,10E)-N-isobutyl-2,4,8,10-dodecatetraenamide, which is newly identified in Asiasarum heterotropoides, were mostly higher in SCRTD than in SCRTM, which was related to the anti-inflammatory effect. From the iNOS inhibition test, it was found that SCRTD had a stronger anti-inflammatory effect than SCRTM. It was demonstrated that multicomponent interactions can be changed by the preparation method, and finally the anti-inflammatory effect in SCRT can be affected.


Assuntos
Medicamentos de Ervas Chinesas , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Interações Medicamentosas , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas/métodos , Camundongos , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
5.
Life Sci ; 217: 212-221, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550883

RESUMO

AIMS: Cerebral ischemia reperfusion (I/R) is a neurovascular disease leading to cerebral damage. It was found that postmenopausal women are liable to more dangerous effects than men at same age in stroke. The objective of this study is to investigate the neuroprotective effect of zeranol against cerebral ischemia reperfusion in ovariectomized rats. MAIN METHODS: 36 female wistar rats divided in to 3 groups: sham group, I/R group (where I/R was induced 7 weeks after ovariectomy), zeranol group (0.5 mg/kg every 3 days for 5 weeks before I/R). Cerebral ischemia reperfusion (I/R) was performed by bilateral common carotid artery occlusion then de-ligated to restore blood flow. After 24 h of reperfusion, rats performed cylinder test to evaluate behavioral dysfunction followed by decapitation. Brain tissues were collected for biochemical measures such as oxidative stress marker malondialdehyde, antioxidant markers reduced glutathione, inflammatory markers (interleukin-1 beta, tumor necrosis factor alpha, and inducible nitric oxide synthase), matrix metalloproteinase-9, adenosine triphosphate, brain derived neurotrophic factor, glucose transporter-3, phosphorylated c-AMP response element binding protein and finally nissl staining for histopathological examination. KEY FINDINGS: The zeranol administered group showed a reversal of neuronal damage caused by ischemia evidenced by the decrease in MDA, IL-1ß, TNF-α, and MMP-9 levels, increase GSH, and ATP levels, decrease expression of iNOS in both regions cortex and hippocampus, increase protein level of p-CREB, GLUT-3 and BDNF, increase number of intact neuron cells in both regions and attenuated histological changes in both cortex and hippocampus regions. SIGNIFICANCE: Zeranol has neuroprotective potential against cerebral ischemia reperfusion in ovariectomized rats.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fitoestrógenos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Zeranol/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Feminino , Mediadores da Inflamação/análise , Mediadores da Inflamação/metabolismo , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/metabolismo , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia
6.
Acta cir. bras ; 34(4): e201900402, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001091

RESUMO

Abstract Purpose: To evaluate the effect of amniotic fluid in liver preservation in organ transplantation, and compare it with standard preservation solutions. Methods: The groups consisted of Group 1: Ringer Lactate (RL) group, Group 2: HTK group, Group 3: UW group, Group 4: AF group. The livers of rats from Group 1, 2, 3, and 4 were perfused and placed into falcon tubes containing RL, HTK, UW, and AF solutions at +4‎°C, respectively. The tubes were stored for 12 hours in the refrigerator at +4°C. Tissue samples were taken at the 6th and 12th hours for histopathological examinations of the perfused livers, and storage solutions for biochemical analyzes at 6th and 12th hours. Results: AF was shown to maintain organ viability by reducing the number of cells undergoing apoptosis. Histopathological changes such as sinusoidal dilatation, hydropic degeneration, and focal necrosis were found to be similar to the groups in which the standard organ preservation solutions were used. Additionally, the results of INOS, IL-10, and TNF-α,which were evaluated immunohistochemically, have been shown to be similar to the UW and HTK groups. Conclusions: AF provided conservation similar to UW and HTK in the 12-hour liver SCS process. The fact that apoptosis values are comparable to standard preservation solutions supports the success of AF in the cold storage of the liver.


Assuntos
Animais , Masculino , Criopreservação/métodos , Soluções para Preservação de Órgãos/farmacologia , Líquido Amniótico , Fígado/irrigação sanguínea , Fígado/patologia , Preservação de Órgãos/métodos , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Valores de Referência , Fatores de Tempo , Sobrevivência de Tecidos , Imuno-Histoquímica , Traumatismo por Reperfusão/prevenção & controle , Distribuição Aleatória , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Interleucina-10/análise , Ratos Wistar , Marcação In Situ das Extremidades Cortadas , Óxido Nítrico Sintase Tipo II/análise , Solução de Ringer/farmacologia , Glucose/farmacologia , Manitol/farmacologia
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(10): 1209-1214, 2018 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-30377131

RESUMO

OBJECTIVE: To investigate the effect of curcumin against cigarette smoke extract (CSE)- induced oxidative stress in human bronchial epithelial cells and explore the underlying mechanism. METHODS: Human bronchial epithelial cell line 16HBE was treated for 24 h with curcumin, CSE, CSE + curcumin, and CSE + curcumin with transfection by a short hairpin RNA targeting PPARγ (shPPARγ). MTT assay was used to observe the changes in the cell viability after the treatments. Quantitative real-time PCR was performed to detect the mRNA expressions of tumor necrosis factor-α (TNF-α), iNOS and PPARγ in the cells, and the protein expressions of iNOS, PPARγ and the phosphorylation of NF-κB p65 were detected using Western blotting. RESULTS: The treatments did not cause significant changes in the cell viability. Exposure to CSE for 24 h significantly lowered PPARγ expression and increased TNF-α and iNOS expressions and phosphorylation of NF-κB p65 in the cells. The effects of CSE were significantly suppressed by curcumin, but transfection of the cells with shRNA-PPARγ obviously abrogated the suppressive effects of curcumin. CONCLUSIONS: Curcumin suppresses CSE-induced oxidative stress and inflammation via the PPARγ/NF-κB signaling pathway in 16HBE cells, suggesting the potential of curcumin in the treatment of chronic obstructive pulmonary disease.


Assuntos
Brônquios/citologia , Curcumina/farmacologia , Células Epiteliais/efeitos dos fármacos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Fumaça , Produtos do Tabaco , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Técnicas In Vitro , NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/metabolismo , PPAR gama/genética , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
8.
Biomed Pharmacother ; 108: 1384-1392, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372841

RESUMO

BACKGROUNDS: The aim of this study was to investigate the oxidative damage and inflammatory effects in the hippocampus and cerebellum in lipopolysaccharide (LPS)-induced sepsis model and possible ameliorating effects of pregabalin (PG). METHODS: Twenty four female Wistar Albino rats (12 month old) were divided into 3 groups as follows: Group I (Control; 0.1 ml/gavage and i.p. saline, single dose), Group II (LPS; 5 mg/kg LPS, i.p, single dose), Group III (LPS + PG; 5 mg/kg LPS, i.p, single dose + 30 mg/kg, gavage, single dose). DNA damage, ischemia-modified albumin (IMA), total oxidant status (TOS), total antioxidant status (TAS) oxidative stress index (OSI), leukocyte (WBC), lymphocyte, neutrophil, hemoglobin (HGB), erythrocyte (RBC), and thrombocyte counts were measured in blood and brain tissues. Histopathological and immunohistochemical evaluation of Caspase- 3, G-CSF, IL-6, SAA, iNOS expressions were conducted using hippocampus and cerebellum tissues. RESULTS: Comet analysis score, lymphocytes, neutrophils, WBC, IMA, TOS and OSI values were increased in Group II compared with to Group I (p < 0.05). IMA levels in blood, TOS and OSI levels in the brain were significantly decreased in Group III compared to Group II (p < 0.05). We observed increased hemorrhages, neutrophils, leukocytes infiltrations and neuron degeneration in Group II compared to Group I. Caspase 3, G-CSF, IL-6, SAA, iNOS expressions were increased in group II compared to Group I (p < 0.001). CONCLUSION: Pregabalin partly ameliorated the damage caused by the exposure to LPS in hippocampus and cerebellum; however, further studies are needed to determine pregabalin's possible protective effects at different doses and with different techniques.


Assuntos
Cerebelo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Pregabalina/farmacologia , Sepse/patologia , Animais , Células Sanguíneas/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/patologia , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Óxido Nítrico Sintase Tipo II/análise , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/metabolismo
9.
Int J Mol Sci ; 19(9)2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30227679

RESUMO

Aberrant nitric oxide synthase 2 (NOS2) expression has been suggested as an interesting therapeutic target that is being implicated as a component of the molecular profile of several human malignant tumors, including glioblastoma, which is the most aggressive brain tumor with limited therapeutic options and poor prognosis. The aim of the present work was to evaluate the effect of 1400W, a specific NOS2 inhibitor, on human glioma cells in terms of clonogenic potential, proliferation, migration rate, and neurosphere generation ability. NOS2 expression was determined by Western blotting. Nitric oxide (NO) production was measured through nitrite level determination. The trypan blue exclusion test and the plate colony formation assay were performed to evaluate cell proliferation and clonogenic potential. Cell proliferation and migration ability was assessed by the in vitro wound-healing assay. Neurosphere generation in a specific stemcell medium was investigated. NOS2 was confirmed to be expressed in both the glioma cell line and a human glioma primary culture, and overexpressed in relative derived neurospheres. Experiments that aimed to evaluate the influence of 1400W on U-87 MG, T98G (glioblastoma cell lines) and primary glioma cells sustained the crucial role played by NOS2 in proliferation, colony formation, migration, and neurosphere generation, thus supporting the emerging relevance of a NOS2/NO system as a prognostic factor for glioma malignancy and recurrence.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioma/patologia , Humanos , Invasividade Neoplásica/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Células Tumorais Cultivadas
10.
Int Immunopharmacol ; 64: 289-297, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30223191

RESUMO

Nicorandil, an antianginal and potassium channel opener agent, has different useful impacts on cardiovascular and respiratory systems. Its effect against silicosis has not been discussed yet, therefore, this is an attempt to decide whether nicorandil can reduce silica-induced lung injury in rats. Silica model was induced by intranasal instillation of silica dust once. Rats were given nicorandil for 56 days after exposure to silica. Results showed that nicorandil significantly alleviated silica-induced inflammation as it decreased the elevated levels of total and differential cell counts, pulmonary edema (revealed by decreased lung/body weight ratio and W/D weight ratio), LDH and total protein levels in BALF. Notably, nicorandil decreased collagen deposition as evidenced by reduction in levels of hydroxyproline and collagen in lung tissues as well as obvious alleviation in silica-induced fibrosis in histopathological findings. Nicorandil effectively reduced the increased expression of NF-κB and iNOS and decreased MPO levels in lung tissues. Moreover, nicorandil abolished oxidative and nitrosative stress via reducing levels of pulmonary MDA and NOx concomitant with elevating levels of pulmonary GSH and SOD. Meanwhile, nicorandil decreased the levels of TNF-α and TGF-ß, up regulated Nrf-2 and HO-1 levels in BALF suggesting antioxidant, anti-inflammatory and antifibrotic properties. In summary, nicorandil can confer protection against silica-induced lung inflammation and fibrosis. This impact might be due to its ability to down regulate the production of inflammatory and fibrotic cytokines in addition to restoring oxidant/antioxidant balance.


Assuntos
Nicorandil/uso terapêutico , Pneumonia/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Silicose/tratamento farmacológico , Animais , Colágeno/análise , Modelos Animais de Doenças , Masculino , Óxido Nítrico Sintase Tipo II/análise , Ratos , Ratos Sprague-Dawley , Silicose/metabolismo , Fator de Crescimento Transformador beta/análise , Fator de Necrose Tumoral alfa/análise
11.
Biochem Biophys Res Commun ; 503(4): 3167-3173, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30149914

RESUMO

The investigation into the potential health risks associated with the use of engineered nanoparticles is a major scientific interest in recent years. The present study elucidated the involvement of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in carboxylated multi-walled carbon nanotubes (MWCNTs)-induced hepatotoxicity. Pubertal rats were exposed to purified MWCNTs at 0, 0.25, 0.50, 0.75 and 1.0 mg/kg for 5 consecutive days. Results indicated that exposure to MWCNTs caused liver damage evidenced by significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) when compared with control. Moreover, MWCNTs significantly decreased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities as well as glutathione level whereas it significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities in liver of the treated rats. Moreover, the dose-dependent increase in hepatic hydrogen peroxide (H2O2) and lipid peroxidation levels were accompanied by marked increase in micronucleated polychromatic erythrocytes (MNPCE) in the MWCNTs-treated rats. Administration of MWCNTs significantly increased serum concentrations of pro-inflammatory cytokines namely interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the treated rats. Immunohistochemical analysis showed significantly increased COX-2 and iNOS protein expressions in the liver of MWCNTs-treated rats. In conclusion, carboxylated MWCNTs induces hepatic damage via disruption of antioxidant defense systems, promotion of pro-inflammatory cytokines generation and expression of COX-2 and i-NOS in rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocinas/imunologia , Fígado/efeitos dos fármacos , Nanotubos de Carbono/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/imunologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Nanotubos de Carbono/química , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/imunologia , Ratos Wistar
12.
Biochem Pharmacol ; 157: 244-257, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30098312

RESUMO

Changes in endogenous cannabinoid homeostasis are associated with both ethanol-related neuroinflammation and memory decline. Extensive research is still required to unveil the role of endocannabinoid signaling activation on hippocampal microglial cells after ethanol exposure. Either microglial morphology, phenotype and recruitment may become notably altered after chronic alcohol-related neurodegeneration. Here, we evaluated the pharmacological effects of fatty-acid amide-hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg), oleoylethanolamide (OEA, 10 mg/kg), arachidonoylethanolamide (AEA, 10 mg/kg), the CB1 receptor agonist ACEA (3 mg/kg) and the CB2 receptor agonist JWH133 (0.2 mg/kg) administered for 5 days in a rat model of subchronic (2 weeks) ethanol diet (11% v/v) exposure. URB597 turned to be the most effective treatment. URB597 increased microglial (IBA-1+) cell population, and changed morphometric features (cell area and perimeter, roughness, fractal dimension, lacunarity) associated with activated microglia in the hippocampus of ethanol-exposed rats. Regarding innate immune activity, URB597 specifically increased mRNA levels of toll-like receptor 4 (TLR4), glial fibrillary acidic protein (Gfap) and the chemokine stromal cell-derived factor 1 (SDF-1α/CXCL12), and elevated the cell population expressing the chemokine receptors CX3CR1, CCR2 and CCR4 in the ethanol-exposed rat hippocampus. Contrary to ethanol effect, URB597 reduced mRNA levels of Iba-1, Tnfα, IL-6 and the monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as cell population expressing iNOS. URB597 effects on hippocampal immune system were accompanied by changes in short and long-term visual recognition memory. These results suggest that FAAH inhibition may modulates hippocampal microglial recruitment and activation that can be associated with improved hippocampal-dependent memory despite ethanol exposure.


Assuntos
Amidoidrolases/antagonistas & inibidores , Benzamidas/farmacologia , Carbamatos/farmacologia , Etanol/toxicidade , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Microglia/efeitos dos fármacos , Animais , Ácidos Araquidônicos/farmacologia , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Giro Denteado/efeitos dos fármacos , Endocanabinoides/farmacologia , Inibidores Enzimáticos/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/análise , Hipocampo/citologia , Hipocampo/imunologia , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Microglia/citologia , Microglia/enzimologia , Óxido Nítrico Sintase Tipo II/análise , Fenótipo , Alcamidas Poli-Insaturadas/farmacologia , Ratos Wistar , Receptores de Quimiocinas/metabolismo
13.
Mycopathologia ; 183(4): 709-716, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29736739

RESUMO

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. These fungi are endemic in the southern USA and northern Mexico. Immunocompromised patients are susceptible to develop severe forms of this fungal infection. Cytokines play an important role in controlling the fungal infection, but little is known about the predominant immunological environment in human lung tissue from fatal cases. Our aim was to analyze the pro-inflammatory and anti-inflammatory cytokines and monocyte/macrophages markers (CD14 and CD206) in the granulomas of six fatal cases of coccidioidomycosis. Cytokines and surface markers were higher in coccidioidomycosis cases when compared to control (P < 0.05). CD14 positive cells were increased inside the coccidioidal granuloma when compared to the outside (P < 0.05). No differences were found in the number of CD206+ cells inside the granuloma when compared to the outer population (P > 0.05). Interestingly, an analysis of stain intensity signals showed an increased signaling of CD14, CD206, IL-10 and TNFα inside the granuloma when compared to the outside (P < 0.05). iNOS and IL-12 gene expression were not detected in coccidioidomycosis cases, while IL-10, IL-6 and TGFß gene expression were detected, but the differences when compared to healthy lungs were not significant (P > 0.05). TNFα gene expression was lower in coccidioidomycosis cases when compared to healthy lung (P = 0.05). In conclusion, pro- and anti-inflammatory responses co-exist inside of the granulomas of fatal cases of coccidioidomycosis and the absent of iNOS and IL-12 gene expression may be related with patient's outcome.


Assuntos
Coccidioidomicose/parasitologia , Granuloma/patologia , Pulmão/patologia , Idoso , Citocinas/análise , Histocitoquímica , Humanos , Lectinas Tipo C/análise , Receptores de Lipopolissacarídeos/análise , Lectinas de Ligação a Manose/análise , México , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/análise , Receptores de Superfície Celular/análise , Estudos Retrospectivos , Estados Unidos
14.
Infect Immun ; 86(7)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29661929

RESUMO

Staphylococcus aureus is a leading cause of device-associated biofilm infections, which represent a serious health care concern based on their chronicity and antibiotic resistance. We previously reported that S. aureus biofilms preferentially recruit myeloid-derived suppressor cells (MDSCs), which promote monocyte and macrophage anti-inflammatory properties. This is associated with increased myeloid arginase-1 (Arg-1) expression, which has been linked to anti-inflammatory and profibrotic activities that are observed during S. aureus biofilm infections. To determine whether MDSCs and macrophages utilize Arg-1 to promote biofilm infection, Arg-1 was deleted in myeloid cells by use of Tie-2Cre mice. Despite Arg-1 expression in biofilm-associated myeloid cells, bacterial burdens and leukocyte infiltrates were similar between wild-type (WT) and Arg-1fl/fl;Tie-2Cre conditional knockout (KO) mice from days 3 to 14 postinfection in both orthopedic implant and catheter-associated biofilm models. However, inducible nitric oxide synthase (iNOS) expression was dramatically elevated in biofilm-associated MDSCs from Arg-1fl/fl;Tie-2Cre animals, suggesting a potential Arg-1-independent compensatory mechanism for MDSC-mediated immunomodulation. Treatment of Arg-1fl/fl;Tie-2Cre mice with the iNOS inhibitor N6-(1-iminoethyl)-l-lysine (l-NIL) had no effect on biofilm burdens or immune infiltrates, whereas treatment of WT mice with the Arg-1/ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) increased bacterial titers, but only in the surrounding soft tissues, which possess attributes of a planktonic environment. A role for myeloid-derived Arg-1 in regulating planktonic infection was confirmed using a subcutaneous abscess model, in which S. aureus burdens were significantly increased in Arg-1fl/fl;Tie-2Cre mice compared to those in WT mice. Collectively, these results indicate that the effects of myeloid Arg-1 are context dependent and are manifest during planktonic but not biofilm infection.


Assuntos
Arginase/fisiologia , Biofilmes , Células Supressoras Mieloides/fisiologia , Plâncton/microbiologia , Infecções Estafilocócicas/etiologia , Staphylococcus aureus/fisiologia , Animais , Poliaminas Biogênicas/fisiologia , Infecções Relacionadas a Cateter , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/análise
15.
Braz J Med Biol Res ; 51(5): e7132, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29561958

RESUMO

Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.


Assuntos
Anti-Inflamatórios/uso terapêutico , Canabidiol/uso terapêutico , Enterite/prevenção & controle , Doenças Fetais/metabolismo , Gastrosquise/metabolismo , Intestinos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Doenças Fetais/patologia , Gastrosquise/patologia , Imuno-Histoquímica , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Nitritos/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley
17.
J Oral Pathol Med ; 47(2): 136-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29108105

RESUMO

BACKGROUND: The prognosis of human malignancies has been shown to depend on immunological parameters, such as macrophage polarization (M1 and M2). In this study, we identify the phenotype of macrophages, and investigate an involvement of infiltrated T cells that participate in the polarization of macrophages, in oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemical method was used to examine the number of CD68+ , CD163+ (M2), iNOS+ (M1) macrophages, and CD4+ , CD8+ , CCR4+ (Th2), CCR5+ (Th1) cells in 102 cases of OSCC: without metastases-OSCC M(-) (n = 54), and with metastases-OSCC M(+) (n = 48), 23 cases of OLK, and 18 control cases. RESULTS: The mean number of CD68+ , CD163+ , iNOS+ , CD4+ , CCR4+ , CCR5+ cells was significantly increased in OSCC M(+) group compared with OLK, OSCC M(-) and control group. We found positive correlations between the number of CD4+ T cells and CD163+ and iNOS+ macrophages as well as CCR4+ and CCR5+ cells in both OSCC groups. The mean number of CD8+ cells was significantly increased in OSCC M(-) and OLK compared with OSCC M(+) and control group. In OSCC M(+) and OSCC M(-) groups, a negative correlation between the number of CD8+ cells and CD163+ and iNOS+ macrophages was found. CONCLUSIONS: The number and co-localization of lymphocytes and macrophages in OLK and OSCC may indicate that infiltrating cells influence the early and subsequent stage of oral carcinogenesis.


Assuntos
Antígenos de Diferenciação de Linfócitos T/análise , Carcinoma de Células Escamosas/patologia , Leucoplasia Oral/patologia , Macrófagos/patologia , Neoplasias Bucais/patologia , Fenótipo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos CD4/análise , Linfócitos T CD4-Positivos , Antígenos CD8/análise , Carcinogênese/patologia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Leucoplasia Oral/química , Leucoplasia Oral/imunologia , Macrófagos/química , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/química , Neoplasias Bucais/imunologia , Estadiamento de Neoplasias , Óxido Nítrico Sintase Tipo II/análise , Prognóstico , Receptores CCR4/análise , Receptores CCR5/análise , Receptores de Superfície Celular/análise , Estudos Retrospectivos , Células Th1
18.
Nitric Oxide ; 72: 41-45, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29129818

RESUMO

Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes. We measured NO levels using the fluorescent probe, diaminofluorescein (DAF-2DA), and flow cytometry in monocytes, neutrophils, and natural killer cells from healthy subjects immediately after blood draw (Time 0) and 30, 60, and 120 min following the blood draw. There was no significant difference among the 4 study time points in NO (DAF-2) levels, though there was wide intra-subject variability at all time points. Using LPS stimulation, we compared iNOS (the more traditional surrogate marker of NO dynamics) with NO (by DAF-2) in natural killer cells and monocytes and, we found no difference in the response patterns. In summary, we did find that within a 2-hour interval from blood draw to sample processing, there was a remarkably wide intra-subject variability in expression of intracellular NO (DAF-2) in leukocytes of healthy individuals at baseline and over time. The mechanism(s) for these differences are not known but could clearly confound efforts to detect changes in NO metabolism in white blood cells. We speculate that rapid pulsatility of NO could explain the wide variability seen.


Assuntos
Leucócitos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Adulto , Análise Química do Sangue/métodos , Calmodulina/metabolismo , Citometria de Fluxo , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Óxido Nítrico/análise , Óxido Nítrico Sintase Tipo II/análise , Fatores de Tempo
19.
Parasite Immunol ; 40(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29130475

RESUMO

Toxoplasmosis is mostly associated with other intestinal parasitic infections especially Giardia due to shared mode of peroral infection. Toxoplasma and Giardia induce a strong T-helper 1- immune response. Our aim was to induce a protective immune response that results in significant impact on intestinal and extra-intestinal phases of Toxoplasma infection. This study was conducted in experimental animals and assessment of Giardia cyst extract effect on Toxoplasma infection was investigated by histopathological examination of small intestine and brain, Toxoplasma cyst count and iNOS staining of the brain, measurement of IFN-γ and TGF-ß in intestinal tissues. Results showed that the brain Toxoplasma cyst number was decreased in mice infected with Toxoplasma then received Giardia cyst extract as compared to mice infected with Toxoplasma only. This effect was produced because Giardia cyst extract augmented the immune response to Toxoplasma infection as evidenced by severe inflammatory reaction in the intestinal and brain tissues, increased levels of IFN-γ and TGF-ß in intestinal tissues and strong iNOS staining of the brain. In conclusion, Giardia cyst extract generated a protective response against T. gondii infection. Therefore, Giardia antigen will be a suitable candidate for further researches as an immunomodulatory agent against Toxoplasma infection.


Assuntos
Antígenos de Protozoários/imunologia , Giardia/imunologia , Giardíase/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/imunologia , Toxoplasmose/terapia , Animais , Encéfalo/parasitologia , Cistos/imunologia , Cistos/parasitologia , Feminino , Giardíase/parasitologia , Inflamação/imunologia , Inflamação/parasitologia , Interferon gama/imunologia , Intestino Delgado/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/análise , Células Th1/imunologia , Toxoplasmose/imunologia , Fator de Crescimento Transformador beta/imunologia
20.
Braz. j. med. biol. res ; 51(5): e7132, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889081

RESUMO

Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.


Assuntos
Animais , Feminino , Gravidez , Ratos , Canabidiol/uso terapêutico , Gastrosquise/metabolismo , Enterite/prevenção & controle , Doenças Fetais/metabolismo , Intestinos/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Imuno-Histoquímica , Ratos Sprague-Dawley , Gastrosquise/patologia , Modelos Animais de Doenças , Óxido Nítrico Sintase Tipo II/análise , Doenças Fetais/patologia , Nitratos/metabolismo , Nitritos/metabolismo
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