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1.
Cytogenet Genome Res ; 158(1): 17-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261155

RESUMO

Osteoarthritis (OA) is a degenerative disease characterized by progressive articular cartilage destruction and joint marginal osteophyte formation with different degrees of synovitis. Docosahexaenoic acid (DHA) is an unsaturated fatty acid with anti-inflammatory, antioxidant, and antiapoptotic functions. In this study, the human chondrosarcoma cell line SW1353 was cultured in vitro, and an OA cell model was constructed with inflammatory factor IL-1ß stimulation. After cells were treated with DHA, cell apoptosis was measured. Western blot assay was used to detect protein expression of apoptosis-related factors (Bax, Bcl-2, and cleaved caspase-3) and mitogen-activated protein kinase (MAPK) signaling pathway family members, including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38 MAPK. Our results show that IL-1ß promotes the apoptosis of SW1353 cells, increases the expression of Bax and cleaved caspase-3, and activates the MAPK signaling pathway. In contrast, DHA inhibits the expression of IL-1ß, inhibits IL-1ß-induced cell apoptosis, and has a certain inhibitory effect on the activation of the MAPK signaling pathway. When the MAPK signaling pathway is inhibited by its inhibitors, the effects of DHA on SW1353 cells are weakened. Thus, DHA enhances the apoptosis of SW1353 cells through the MAPK signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-1beta/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Butadienos/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Interleucina-1beta/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/biossíntese , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Nitrilos/farmacologia , Inibidores de Proteínas Quinases/farmacologia
2.
Cell Physiol Biochem ; 52(3): 486-502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873823

RESUMO

BACKGROUND/AIMS: Cross-talk between different pancreatic islet cell types regulates islet function and somatostatin (SST) released from pancreatic delta cells inhibits insulin secretion from pancreatic beta cells. In other tissues SST exhibits both protective and pro-apoptotic properties in a tissue-specific manner, but little is known about the impact of the peptide on beta cell survival. Here we investigate the specific role of SST in the regulation of beta cell survival in response to physiologically relevant inducers of cellular stress including palmitate, cytokines and glucose. METHODS: Pancreatic MIN6 beta cells and primary mouse islet cells were pre-treated with SST with or without the Gi/o signalling inhibitor, pertussis toxin, and exposed to different cellular stress factors. Apoptosis and proliferation were assessed by measurement of caspase 3/7 activity, TUNEL and BrdU incorporation, respectively, and expression of target genes was measured by qPCR. RESULTS: SST partly alleviated upregulation of cellular stress markers (Hspa1a and Ddit3) and beta cell apoptosis in response to factors such as lipotoxicity (palmitate), pro-inflammatory cytokines (IL1ß and TNFα) and low glucose levels. This effect was mediated via a Gi/o protein-dependent pathway, but did not modify transcriptional upregulation of the specific NFκB-dependent genes, Nos2 and Ccl2, nor was it associated with transcriptional changes in SST receptor expression. CONCLUSION: Our results suggest an underlying protective effect of SST which modulates the beta cell response to ER stress and apoptosis induced by a range of cellular stressors associated with type 2 diabetes.


Assuntos
Proliferação de Células/efeitos dos fármacos , Glucose/antagonistas & inibidores , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Toxina Pertussis/antagonistas & inibidores , Somatostatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Caspase 7/genética , Caspase 7/metabolismo , Linhagem Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulação da Expressão Gênica , Glucose/farmacologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/farmacologia , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ácido Palmítico/antagonistas & inibidores , Ácido Palmítico/farmacologia , Toxina Pertussis/farmacologia , Técnicas de Cultura de Tecidos , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia
3.
Biomed Pharmacother ; 112: 108610, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30797145

RESUMO

Osteoarthritis (OA) is a common degenerative joint disease, which is closely related to cartilage degradation. Anthocyanins, a natural flavonoid pigments, exhibit strong antioxidant and anti-inflammatory properties. However, the effect of anthocyanin on inflammatory response in OA has not been investigated. Our results showed that cyanidin-3-O-glucoside (C3G) and peonidin-3-O-glucoside (P3G), the main anthocyanins found in three Thai purple rice cultivars, attenuated the inhibition of porcine cartilage degradation in an experimental model. The effects of three Thai purple rice extracts were related to their high concentration of anthocyanins. Moreover, protocatechuic acid (PA), the main metabolite of anthocyanin, has chondroprotective potential by reducing glycosaminoglycans and collagen breakdown in IL-1ß/OSM-induced porcine cartilage explants in long-term condition. The induction of matrix metalloproteinases (MMPs) caused by IL-1ß-stimulated human chondrocytes was also attenuated by C3G, P3G, and their metabolites. Furthermore, C3G, P3G, and their metabolites pretreatment significantly inhibited IκBα degradation, the level of p-p65, and ERK/MAPK pathway. Additionally, PA pretreatment enhanced the phosphorylation of JNK in IL-1ß-stimulated human chondrocytes. These findings indicated that anthocyanin in Thai purple rice exhibited anti-inflammatory effects in IL-1ß-stimulated human chondrocytes by inhibiting NF-κB and ERK/MAPK signaling pathway.


Assuntos
Antocianinas/farmacologia , Condrócitos/metabolismo , Interleucina-1beta/toxicidade , Sistema de Sinalização das MAP Quinases/fisiologia , Metaloproteinases da Matriz/biossíntese , NF-kappa B/metabolismo , Oryza , Animais , Antocianinas/isolamento & purificação , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Humanos , Interleucina-1beta/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Suínos
4.
Basic Res Cardiol ; 114(2): 11, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30673858

RESUMO

Coxsackieviruses of group B (CVB) are well-known causes of acute and chronic myocarditis. Chronic myocarditis can evolve into dilated cardiomyopathy (DCM) characterized by fibrosis and cardiac remodeling. Interleukin-1ß (IL-1ß) plays a decisive role in the induction of the inflammatory response as a consequence of viral replication. In this study, we analyzed the effects of IL-1ß neutralization on the transition of acute to chronic myocarditis in a mouse model of CVB3 myocarditis. Mice were treated with an anti-murine IL-1ß antibody as a surrogate for Canakinumab at different time points post CVB3 infection. Treatment was performed in the early phase (day 1-14 pi, day 3-14 pi) or at a later stage of myocarditis (day 14-28 pi). Subsequently, the hearts were examined histologically, immunohistochemically and by molecular biology. A significant reduction of viral replication, cardiac damage and inflammation was found after administration of the antibody in the early phase and in the later phase of infection. Furthermore, less collagen I deposition and a considerable reduction of fibrosis were found in antibody-treated mice. Using microarray analysis, a significant upregulation of various extracellular matrix and fibrosis-associated molecules was found in CVB3-infected mice, including TGF-ß, TIMP-1 and MMP12, as well as diverse matricellular proteins, whereas, these molecules were significantly downregulated in all IL-1ß antibody-treated infected mice. Neutralization of IL-1ß at different stages of enteroviral infection prevents the development of chronic viral myocarditis by reducing inflammation, interstitial fibrosis and adverse cardiac remodeling. These findings are relevant for the treatment of patients with acute and chronic myocarditis.


Assuntos
Interleucina-1beta/antagonistas & inibidores , Miocardite/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Doença Crônica , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/patologia , Enterovirus Humano B , Camundongos , Miocardite/metabolismo , Miocardite/virologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
5.
Mol Med Rep ; 19(2): 1024-1031, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569107

RESUMO

Diabetic retinopathy (DR) is a retinal disease caused by metabolic disorders of glucose tolerance that can lead to irreversible blindness if not adequately treated. Retinal pigment epithelial cell (RPEC) dysfunction contributes to the pathogenesis of DR. In the present study the anti­inflammatory effect of curcumin (CUR) was investigated in RPECs damaged by high glucose levels. RPEC treated with 30 mmol/l glucose was regarded as high glucose group, and cells treated with 24.4 mmol/l mannitol was set as equivalent osmolarity group. Cell Counting Kit­8 assay was used to measure RPEC viability, the expression of phosphorylated (p)­AKT and p­mammalian target of rapamycin (mTOR) were assessed by western blot, and secretion of tumor necrosis factor (TNF)­α, interleukin (IL)­6 and IL­1ß in the culture medium was measured by ELISA. Intracellular reactive oxygen species (ROS) levels were measured by laser scanning confocal microscope. The present data indicated that, compared with mannitol treatment, high glucose treatment reduced RPEC viability, increased TNF­α, IL­6 and IL­1ß secretion, increased ROS formation and promoted phosphorylation of AKT and mTOR. The antioxidant N­acetylcysteine, the phosphoinositide 3­kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. In addition, pretreatment with 10 µmol/l CUR reduced secretion levels of TNF­α, IL­6 and IL­1ß, ROS formation and phosphorylation of AKT and mTOR. In conclusion, CUR inhibited high glucose­induced inflammatory injury in RPECs by interfering with the ROS/PI3K/AKT/mTOR signaling pathway. The present study may reveal the molecular mechanism of CUR inhibition effects to high glucose­induced inflammatory injury in RPEC.


Assuntos
Anti-Inflamatórios/farmacologia , Curcumina/farmacologia , Células Epiteliais/efeitos dos fármacos , Glucose/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Cromonas/farmacologia , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Sinergismo Farmacológico , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Glucose/toxicidade , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Modelos Biológicos , Morfolinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Biosci Biotechnol Biochem ; 83(4): 598-604, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30582416

RESUMO

The aim of this study was to investigate the effects and underlying mechanisms of calcitonin (CT) on interleukin 1 beta (IL-1ß) stimulated human chondrocytes. IL-1ß (5 ng/mL) was added into chondrocytes to establish osteoarthritis (OA) model in vitro. Different concentrations of CT (0.1, 0.5, 1, 5, 10 and 50 nM) were used for treating IL-1ß stimulated chondrocytes. Cell viability of chondrocytes was measured by cell counting kit-8 (CCK8) method. Western blotting was performed to evaluate the expression of matrix metalloproteinases (MMP-13), tissue inhibitor of metalloproteinases 1 (TIMP-1), p50 and p38. CT inhibited MMP-13 expression and promoted TIMP-1 expression in the IL-1ß stimulated human chondrocytes. The CT-mediated alteration of MMP-13/TIMP-1 ratio was partially attributed to the inactivation of the p50- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing p50 in IL-1ß stimulated chondrocytes. CT might play a protective role in IL-1ß stimulated OA model via p50-NF-κB pathway. Abbreviations: CT: calcitonin; IL-1ß: interleukin-1ß; MMP-13: matrix metalloproteinases-13; TIMP-1: tissue inhibitors of metalloproteinases-1.


Assuntos
Anti-Inflamatórios/farmacologia , Calcitonina/farmacologia , Condrócitos/efeitos dos fármacos , Interleucina-1beta/antagonistas & inibidores , Metaloproteinase 13 da Matriz/genética , Subunidade p50 de NF-kappa B/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/farmacologia , Metaloproteinase 13 da Matriz/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Proc Natl Acad Sci U S A ; 116(4): 1361-1369, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30545915

RESUMO

Interleukin-1ß (IL-1ß) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1ß during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1ß-deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1ß-deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1ß-deficient mice result in a relatively high percentage of CD11b+ dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1ß-deficient mice, IL-12 secretion by CD11b+ DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1ß-deficient mice includes activated CD8+ lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti-IL-1ß or anti-PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti-IL-1ß Abs followed by anti-PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1ß as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1ß facilitates checkpoint inhibition.


Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Interleucina-1beta/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Antígeno CD11b/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fatores Estimuladores de Colônias/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Feminino , Granzimas/farmacologia , Humanos , Imunossupressão/métodos , Inflamação/metabolismo , Interferon gama/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-30189257

RESUMO

Environmental exposure to arsenic is known to induce immunotoxicity. Macrophages are the professional phagocytes that are important in the immune system. In this study, we utilized the macrophages derived from the THP-1 human monocyte cell line as the experimental model to study the functional suppression induced by arsenite (As+3), one of the most prevalent forms of inorganic arsenic, at environmentally-relevant concentrations. Apoptosis was observed in the THP-1 derived macrophages treated with 500 nM As+3 for 18 h. Suppression of phagocytosis was induced by 18 h As+3 treatment starting from 100 nM. Suppressive effects on the production of two pro-inflammatory cytokines, IL-1ß and TNF-α, were also found with the treatment of low to moderate doses of As+3 in lipopolysaccharides-stimulated THP-1 derived macrophages. The nitric oxide production was also inhibited by As+3 treatments, which was negatively correlated with the production of superoxide. Collectively, the results from the study demonstrated that environmentally-relevant concentrations of As+3 induced cytotoxicity and suppressed the major cellular functions in THP-1 derived macrophages. The macrophages were showed to be relatively sensitive to As+3, and could be the essential target of the toxicity induced by environmental arsenic exposures.


Assuntos
Apoptose/efeitos dos fármacos , Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Imunossupressão , Macrófagos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Fagocitose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Concentração Osmolar , Superóxidos/agonistas , Superóxidos/metabolismo , Células THP-1 , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
9.
Rev. int. androl. (Internet) ; 16(3): 87-94, jul.-sept. 2018. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-178033

RESUMO

It has been reported in the literature that proinflammatory interleukin-1 beta (IL-1β) is increased in cases of testicular ischemia reperfusion (I/R) damage. This information suggests that anakinra, an IL-1β antagonist, may be effective in testicular I/R damage. Objective: In our study, we investigated the effect of anakinra on testicular I/R damage induced in rats with torsion/detorsion. Methods: The 50mg/kg anakinra+testicular torsion/detorsion (KTD-50) and 100mg/kg anakinra+testicular torsion/detorsion (KTD-100) groups received an intraperitoneal (i.p.) injection of 50mg/kg and 100mg/kg of anakinra, respectively. In turn, the testicular torsion/detorsion (TTD) and sham operation (SOG) groups received a single dose of distilled water as a solvent 1h before ketamine anaesthesia. After the testes of the TTD, KTD-50 and KTD-100 groups were subjected to torsion and detorsion for 4h each, the rats were killed with a high-dose anaesthesia, and their testicles were removed and evaluated through biochemical, gene expression and histopathological examinations. The results were evaluated in comparison with those of the SOG group. Results: The levels of malondialdehyde (MDA), myeloperoxidase (MPO) and IL-1β showed significant increases in the TTD group, which underwent torsion/detorsion, compared to the KTD-50, KTD-100 and SOG groups. Conversely, the levels of glutathione (tGSH), glutathione peroxidase (GPO) and glutathione s-transferase (GST) were found to be significantly higher in the KTD-50, KTD-100 and SOG groups than in the TTD group. Conclusion: Anakinra at a 100mg/kg dose histologically suppressed better oxidative stress and tunica albuginea, germ cell, seminiferous tubule and interstitial damage in the testicular tissue compared to a 50mg/kg dose. Experimental results indicate that anakinra might be beneficial in the attenuation of testicular I/R damage


Antecedentes: Se ha reportado en la literatura que citoquinas interleuquina-1 beta (IL-1β) es mayor en el daño de la isquemia reperfusión testicular (I/R). Esta información sugiere que la anakinra, que es un antagonista IL-1β puede ser eficaz en daño testicular I/R. Objetivo: En nuestro estudio se investigó el efecto de este medicamento en daño testicular I/R inducida en ratas con detorsion/torsión. Métodos: KTD-50 grupo recibido intraperitonealmente (i.p.) inyección de 50mg/kg y KTD-100 Grupo 100mg/kg de anakinra, mientras TTD (control) y SOG (sham grupo operación) recibieron una dosis única de agua destilada como solvente, una hora antes de ketamina anestesia. Después de que los testículos de TTD, KTD-50 y KTD-100 grupos fueron sometidas a torsión y detorsion para cuatro por cuatro horas, las ratas fueron asesinados con altas dosis de anestesia, sus testículos fueron extraídos y evaluados a través de la expresión génica, bioquímicas e histopatológicas de exámenes. Los resultados fueron evaluado en comparación con la de SCG grupo. Resultados: Los niveles de MDA, MPO y IL- 1β mostraron incrementos significativos en el grupo TTD/torsión detorsion administrados frente a-50, KTD KTD-100 y SOG grupos. Por el contrario, los niveles de tGSH, GPO y GST resultaron significativamente más altas en KTD-50 KTD-100 y grupos SOG de TTD en grupo. Conclusión: La anakinra en 100mg/kg dosis mejor histológicamente suprime el estrés oxidativo y la túnica albuginea, células germinales, túbulos seminíferos apretadamente enrollados intersticial y daño en el tejido testicular en comparación con la dosis de 50mg/kg. Los resultados experimentales indican que la anakinra puede ser beneficiosa en la atenuación de los daños I/R testicular


Assuntos
Animais , Ratos , Interleucina-1beta/antagonistas & inibidores , Traumatismo por Reperfusão , Estresse Oxidativo , Doenças Testiculares/tratamento farmacológico , Modelos Animais de Doenças , Peroxidase/fisiologia , Glutationa/análise , Glutationa Peroxidase/fisiologia , Expressão Gênica/fisiologia
10.
Mol Vis ; 24: 509-517, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30090014

RESUMO

Purpose: The aim of this study was to investigate the roles of chitosan in inflammation and adipogenesis of primary cultured orbital fibroblasts in Graves ophthalmopathy (GO). Methods: Cell viability, apoptosis, and cell cycle were determined with the Cell Counting Kit-8 (CCK-8), the Annexin V-FITC/PI kit, and flow cytometry, respectively. Inflammation of orbital fibroblasts was stimulated by interleukin-1 beta (IL-1ß). The levels of IL-6 and prostaglandin E-2 (PGE-2) were measured using an enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) was measured with real-time PCR and western blot assay. Phosphorylation of c-Jun N-terminal kinase (JNK) was evaluated with western blot assay. An inhibitor of JNK was used to investigate the signal transduction pathway of cytokine production. Orbital fibroblasts differentiated to adipose cells in differentiation medium. Adipose cells were dyed with Oil Red O. FABP4, adiponectin, C/EBPα, PPAR-γ, and phosphorylation of AKT were evaluated with western blot assay. Results: The results showed that IL-1ß statistically significantly increased the expression of IL-6, PGE-2, and COX-2 in orbital fibroblasts. Phosphorylation of JNK was promoted by IL-1ß. IL-6 and PGE-2 were modulated by the JNK signaling pathway as determined with the inhibition experiments. Chitosan downregulated expression of IL-1ß-stimulated IL-6, COX-2, and PGE-2 and downregulated phosphorylation of JNK. Chitosan inhibited the production of adipose cells dyed by Oil Red O. Chitosan statistically significantly decreased the protein levels of FABP4, adiponectin, C/EBPα, and PPAR-γ with downregulation of AKT phosphorylation during adipocyte differentiation. Conclusions: Chitosan statistically significantly inhibits inflammation and adipogenesis, as well as related signaling pathways, of orbital fibroblasts in GO. This indicates a possible therapeutic effect of chitosan on Graves ophthalmopathy.


Assuntos
Adipócitos/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Quitosana/farmacologia , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Oftalmopatia de Graves/genética , Adipócitos/metabolismo , Adipócitos/patologia , Adiponectina/genética , Adiponectina/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Dinoprostona/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Oftalmopatia de Graves/metabolismo , Oftalmopatia de Graves/patologia , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Pessoa de Meia-Idade , Órbita/efeitos dos fármacos , Órbita/metabolismo , Órbita/patologia , PPAR gama/genética , PPAR gama/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
11.
N Engl J Med ; 378(20): 1908-1919, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29768139

RESUMO

BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS: At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P<0.001), 35% versus 6% of those with mevalonate kinase deficiency (P=0.003), and 45% versus 8% of those with TRAPS (P=0.006). The inclusion of patients whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71% of those with colchicine-resistant familial Mediterranean fever, 57% of those with mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended dosing regimen (every 8 weeks) maintained disease control in 46% of patients with colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase deficiency, and 53% of those with TRAPS. Among patients who received canakinumab, the most frequently reported adverse events were infections (173.3, 313.5, and 148.0 per 100 patient-years among patients with colchicine-resistant familial Mediterranean fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively), with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years). CONCLUSIONS: In this trial, canakinumab was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and TRAPS. (Funded by Novartis; CLUSTER ClinicalTrials.gov number, NCT02059291 .).


Assuntos
Anticorpos Monoclonais/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Interleucina-1beta/antagonistas & inibidores , Deficiência de Mevalonato Quinase/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Adulto Jovem
12.
Bratisl Lek Listy ; 119(4): 198-200, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29663815

RESUMO

Autoinflammatory disorders (AID) are characterized by spontaneous attacks of acute inflammation with a broad spectrum of clinical symptoms. Ongoing inflammation and reoccurrence of acute flares can lead to the development of amyloidosis. One group of AID is represented by monogenic periodic fever syndromes while familial Mediterranean fever (FMF) is the most common form of AID from this group. Its prevalence in Central and Eastern Europe was reported to be very low. We report a case of FMF patient with a very severe clinical course of FMF and intolerance to colchicine, which is a gold standard for FMF treatment. The clinical effect of the application of anakinra was insufficient and accompanied with side effects and low tolerability. Switching to canakinumab (human monoclonal antibody against IL-1ß) at dose of 150 mg every 4 weeks induced a rapid remission of the disease activity and inflammatory markers. However, due to relapse of acute flares after three weeks from application, the escalation of dose to 300 mg every 4 weeks induced a complete remission of symptoms and significantly improved the quality of life. This is the first report of successful canakinumab administration in FMF patient in Central and Eastern Europe, a region with very low incidence of FMF (Tab. 1, Ref. 16).


Assuntos
Anticorpos Monoclonais/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Adulto , Colchicina/uso terapêutico , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1beta/antagonistas & inibidores , Masculino , Qualidade de Vida , Indução de Remissão , Eslováquia , Falha de Tratamento
13.
Lipids Health Dis ; 17(1): 94, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29685140

RESUMO

BACKGROUND: This study examined the effects of chronic alcohol consumption in the rat erythrocytes membrane as well as the involvement of reactive oxygen species and proinflammatory cytokines in its pathogenicity in rats and evaluated the ameliorating effects of myrtle berries seeds aqueous extract (MBSAE). METHODS: Fifty adult male Wistar rats were equally divided into five groups and treated daily for two months as follows: control, ethanol (3 g kg- 1 b.w., p.o.), and ethanol + MBSAE (25, 50 and 100 mg kg- 1, b.w., p.o.). RESULTS: Exposure of rats to alcohol caused significant changes of some haematological parameters, enhanced erythrocytes hemolysis as well as an overproduction of reactive oxygen species such as H2O2, OH• radical and superoxide anion, hence the increase of lipoperoxidation and the depletion of antioxidant enzymes activity as well as non-enzymatic antioxidant (-SH groups and GSH) levels. On the other hand, ethanol intoxication caused the increase of serum TNFα, IL-8, IL-6 and 1Lß, markers of tissue inflammation. However, treatment with MBSAE alleviated all the deleterious effects of alcohol consumption. CONCLUSIONS: MBSAE possess active compounds, which exert marked protective effects in chronic alcohol intoxication, possibly by regulating the erythrocytes osmotic stability as well as antioxidant and inflammatory mediators.


Assuntos
Alcoolismo/prevenção & controle , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Etanol/antagonistas & inibidores , Glutationa/agonistas , Myrtus/química , Alcoolismo/genética , Alcoolismo/metabolismo , Alcoolismo/fisiopatologia , Animais , Antioxidantes/isolamento & purificação , Etanol/toxicidade , Regulação da Expressão Gênica , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/antagonistas & inibidores , Radical Hidroxila/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/antagonistas & inibidores , Interleucina-8/genética , Interleucina-8/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Ratos , Ratos Wistar , Sementes/química , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Toxicol Appl Pharmacol ; 344: 56-73, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29522792

RESUMO

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been associated with conflicting effects within the central nervous system (CNS), with underlying mechanisms remaining unclear. Although differences between individual statins' CNS effects have been reported clinically, few studies to date have compared multiple statins' neuroprotective effects. This study aimed to compare six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin; 0-100 µM) using an in vitro model of lipopolysaccharide (LPS)-induced neuroinflammation and subsequent neurodegeneration. To achieve this, HAPI microglia were treated with LPS (0.1 µg/mL; 24 h), resulting in increased reactive oxygen species (ROS), nitric oxide, and IL-1ß, TNF-α and PGE2 release. Conditioned media ("HAPI-CM") was then transferred to SH-SY5Y neuroblastoma cells, and effects on cellular viability, mitochondrial membrane permeability, apoptosis, autophagy and ROS production assessed. Of the statins investigated, only atorvastatin, pravastatin and rosuvastatin protected SH-SY5Y cells from LPS-induced decreases in cellular viability; this appeared mediated through reduced caspase 3/7 activation and was associated with decreased IL-1ß (atorvastatin, pravastatin) and/or TNF-α (atorvastatin, pravastatin, rosuvastatin). Only pravastatin conferred protection at all tested concentrations. ROS production and autophagic vacuole formation was decreased by all statins, suggesting these two mechanisms are unlikely to be sole mediators of neuroprotection seen with selected statins. Ultimately, our model suggests that despite all statins reducing microglial inflammation, subsequent effects on neuronal viability and cell death signalling pathways varies between statins. Our findings highlight the need to consider individual statins as inducing discrete pharmacological effects within the CNS in future in vitro/in vivo studies and in clinical practice.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Degeneração Neural/metabolismo , Neuroproteção/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Microglia/efeitos dos fármacos , Microglia/metabolismo , Degeneração Neural/tratamento farmacológico , Neuroproteção/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
Eur J Med Chem ; 149: 129-138, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29499485

RESUMO

Twenty-eight compounds with a new scaffold were designed and synthesized by assembling fragments derived from known agents such as stilbenes and piperazinyl pyrimidines. Many strategies have been explored to improve the druggability of these series of compounds, such as increasing the distance between two benzene rings in the scaffold and introducing functional groups at designated positions. These compounds were validated for their anti-neuroinflammatory activity in BV2 cells. Experimental results reveal that the most active compound 8b can inhibit nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) production with IC50 values of 1.0, 2.6, and 0.5 µM, respectively. The compound can also significantly modulate the MAPK pathways through inhibiting the phosphorylation of JNK, ERK1/2, and p38 MAPK without disturbing NF-κB pathway. Parallel artificial membrane permeation assay demonstrated that the most active compound can overcome the blood-brain barrier (BBB). Therefore, this compound can be a promising lead for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/síntese química , Doença de Alzheimer/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Sistema Nervoso Central/patologia , Desenho de Drogas , Humanos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Fosforilação/efeitos dos fármacos , Pirimidinas/síntese química , Estilbenos/síntese química , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese
17.
Clin Exp Rheumatol ; 36(4): 668-675, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29533755

RESUMO

OBJECTIVES: To describe the efficacy, safety, and exposure-response relationship of canakinumab in a subgroup of patients with systemic juvenile idiopathic arthritis (SJIA) aged ≥16 years, representative of adult-onset Still's disease (AOSD) patients, and to compare this subgroup with those of children and young adolescents with SJIA by pooling clinical data collected during the development programme of canakinumab. METHODS: Safety and efficacy data on canakinumab-treated patients were pooled from 4 SJIA studies (NCT00426218, NCT00886769, NCT00889863, and NCT00891046). In the majority of patients, canakinumab was administered at 4 mg/kg every 4 weeks. Efficacy parameters (adapted American College of Rheumatology [aACR] paediatric and juvenile idiopathic arthritis [JIA] ACR responses), quality of life, C-reactive protein levels, safety, and exposure-response relationship were assessed over 12 weeks in 3 age groups (children 2-<12, young adolescents 12-<16 and older adolescents and young adults ≥16 years). RESULTS: Efficacy outcomes were analysed in 216 children, 56 young adolescents and 29 older adolescents and young adults. Efficacy parameters across 3 age groups were largely comparable. At Day 15, at least 50% of patients from each age group exhibited aACR ≥70 and ACR responses. The safety profile of canakinumab was similar across age groups. One death was reported. CONCLUSIONS: Pooled analyses from SJIA studies indicate that older adolescents and young adults SJIA patients show similar efficacy, safety, and exposure-response relationship on a weight-based dosing regimen as observed in children and adolescent SJIA patients. These analyses suggest that canakinumab may be an effective therapy in young adults with Still's disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Interleucina-1beta/antagonistas & inibidores , Doença de Still de Início Tardio/tratamento farmacológico , Adolescente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Criança , Pré-Escolar , Feminino , Humanos , Masculino
18.
J Pharm Pharmacol ; 70(6): 713-722, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29492971

RESUMO

OBJECTIVES: The effects of anti-inflammatory glucocorticoids dexamethasone (DX) and hydrocortisone (HC), pro-inflammatory cytokine interleukin-1ß (IL-1ß) and dietary long-chain polyunsaturated fatty acids (PUFAs) on expression and activity of the ATP-binding cassette transporter P-glycoprotein (P-GP) were studied in porcine brain endothelial cells (PBECs). METHODS: Primary PBECs were treated for 24 h with glucocorticoids, IL-1ß and long-chain PUFAs. P-GP activity was determined by measuring intracellular calcein accumulation and P-GP expression by Western blotting. The effect of PUFAs on membrane fluidity was assessed by fluorescence recovery after photobleaching (FRAP). KEY FINDINGS: Dexamethasone, HC and IL-1ß significantly increased P-GP expression and activity. The effect of IL-1ß was attenuated by the IL-1 receptor antagonist (IL-1RA). This is the first report of the combined actions of IL-1ß and IL-1RA on P-GP expression and the first evidence of glucocorticoid-mediated P-GP up-regulation in PBECs. Arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentenoic acid (EPA) significantly decreased P-GP activity without affecting expression or membrane fluidity. AA, DHA and EPA counteracted IL-1ß-mediated increases in P-GP activity, while AA and EPA, but not DHA, counteracted glucocorticoid-mediated increase in P-GP activity. CONCLUSIONS: While glucocorticoids and IL-1ß possess opposing actions in inflammation, they demonstrate functional consistency by increasing P-GP expression and activity in PBECs.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Barreira Hematoencefálica/metabolismo , Dexametasona/farmacologia , Ácidos Graxos Insaturados/farmacologia , Hidrocortisona/farmacologia , Interleucina-1beta/farmacologia , Animais , Células Cultivadas , Células Endoteliais/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/antagonistas & inibidores , Fluidez de Membrana/efeitos dos fármacos , Ratos , Suínos
19.
Inflammation ; 41(3): 751-759, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29427162

RESUMO

Fibroblast growth factor 21 (FGF-21) has been previously judged as a major metabolic regulator. In this paper, we show that FGF-21 has a potential role in anti-inflammation and immunoregulation. In vivo, treatment with exogenous FGF-21 can alleviate LPS-induced inflammation. In vitro, FGF-21 inhibited LPS-induced IL-1ß expression in THP-1 cells. Furthermore, besides the NF-κB pathway, the mechanism of action of FGF-21 was observed to involve the elevation of IL-10 in the ERK1/2 pathway. This study clearly indicates that FGF21 can be used as an attractive target for the management of inflammatory disorders. This piece of research indicates that FGF-21 could have much value in the management of inflammatory disorders.


Assuntos
Fatores de Crescimento de Fibroblastos/farmacologia , Inflamação/tratamento farmacológico , Interleucina-10/metabolismo , Linhagem Celular , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Inflamação/induzido quimicamente , Interleucina-10/farmacologia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
20.
Neurochem Res ; 43(4): 806-820, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29392519

RESUMO

Neuroinflammation and oxidative stress play an important role in cognition deficit following chronic cerebral hypoperfusion (CCH). Luteolin, a natural flavonoid found in many plants, is known for a variety of pharmacological activities, such as its anti-inflammatory, anti-allergy, urate, anti-tumor, antibacterial, and antiviral effects. To assess whether luteolin could prevent CCH-induced cognitive dysfunction, through its anti-inflammatory and anti-oxidative-stress effects, we used enzyme-linked immunosorbent assays, enzyme activity assays, behavioral methods, immunohistochemistry, and electrophysiology to detect neuroinflammation and oxidative stress, cognition alterations, and long-term potential (LTP), in a bilateral common carotid arteries ligation (2VO) rat model. We demonstrated that CCH increased tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Further, it caused microglia over-activation and astrogliosis, learning and short-term memory dysfunction, and an LTP deficit. Luteolin treatment reversed CCH-induced changes. Specifically, luteolin prevented the increase of TNF-α and IL-1ß, IL-6, and MDA, improved the activity of SOD and GPx, inhibited microglia over-activation and astrogliosis (particularly in the hippocampus and cortex), and ameliorated learning and short-term memory dysfunction, and LTP deficit. Thus, our study suggested that luteolin could be a preferable anti-inflammatory agent to protect cognitive function and synaptic plasticity following CCH. Luteolin could also be putative therapeutic candidate for other inflammation-related brain diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Luteolina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Luteolina/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
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