RESUMO
Vanadyl sulfate (VS), is a component of some food supplements and experimental drugs. This study was carried out to present a novel method for induction of Type 2 diabetes in rats, then for the first time in literature, for evaluating the effect of VS on metabolic parameters and gene expression, simultaneously. 40 male wistar rats were distributed between the four groups, equally. High fat diet and fructose were used for diabetes induction. Diabetic rats treated by two different dose of VS for 12 weeks. Metabolic profiles were evaluated by commercial available kits and gene expression were assayed by real time-PCR. Compared to controls, in non-treated diabetic rats, weight, glucose, triglyceride, total cholesterol, insulin and insulin resistance were increased significantly (p-value <0.05) that indicated induction of type 2 diabetes. Further, the results showed that VS significantly reduced weight, insulin secretion, Tumor Necrosis Factor-alpha (TNF-α) genes expression, lipid profiles except HDL that we couldn't find any significant change and increased Peroxisome Proliferator-Activated Receptor- gamma (PPAR-γ) gene expression in VS-treated diabetic animals in comparison with the non-treated diabetics. Our study demonstrated that vanadyl supplementation in diabetic rats had advantageous effects on metabolic profiles and related gene expression.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , PPAR gama , Fator de Necrose Tumoral alfa , Compostos de Vanádio , Animais , Ratos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/sangue , Resistência à Insulina , PPAR gama/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , Ratos Wistar , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Compostos de Vanádio/farmacologiaRESUMO
OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.
Assuntos
Artroplastia do Joelho , Betametasona , Nervo Femoral , Bloqueio Nervoso , Ropivacaina , Humanos , Administração Intravenosa , Amidas/efeitos adversos , Anestésicos Locais/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Nervo Femoral/efeitos dos fármacos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Ropivacaina/administração & dosagem , Solução Salina/farmacologia , Solução Salina/uso terapêutico , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Betametasona/administração & dosagem , Interleucina-1beta/sangue , Interleucina-1beta/efeitos dos fármacosRESUMO
SUMMARY: The therapeutic effect of a granulocyte-colony stimulating factor (G-CSF) biosimilar drug, zarzio, on non-alcoholic fatty liver disease (NAFLD) in a rat model was investigated in this study. Thirty-two rats were randomly divided into four groups. Groups I and II were fed a standard laboratory diet, whereas groups III and IV were fed a high fat diet (HFD) for 14 weeks. After 12 weeks of feeding, groups I and III were administered normal saline, and groups II and IV were intraperitoneally administered zarzio (200 mg/kg/day) for two consecutive weeks. Hematoxylin-eosin (H&E) staining was used to assess hepatic and pancreatic morphology in all groups, oil red O (ORO) staining for lipid accumulation, Masson's staining for fibrosis, and immunohistochemistry assay for hepatic protein expression of insulin receptor substrate 1 (IRS1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumour necrosis factor alpha (TNF-α) and pancreatic caspase-3. The NAFLD rats (group III) developed hepatic steatosis with increased lipid accumulation, perisinusoidal fibrosis, upregulated IRS1, TNF-α (all P<0.05) without a significant increase in Nrf2 protein expression compared with normal control. In comparison, model rats treated with zarzio (group IV) showed significant rejuvenation of the hepatic architecture, reduction of fat accumulation, and fibrosis. This was accompanied by the upregulation of Nrf2, downregulation of IRS1 and TNF-α protein expression (all P<0.05). No correlation was detected between NAFLD and non-alcoholic fatty pancreas disease (NAFPD). However, the pancreatic β-cells in group III showed increased caspase-3 expression, which was decreased (P<0.05) in group IV. In conclusion, zarzio ameliorates NAFLD by improving the antioxidant capacity of liver cells, reducing hepatic IRS1, TNF-α protein expression and pancreatic β-cells apoptosis, suggesting that zarzio could be used as a potential therapy for NAFLD.
En este estudio se investigó el efecto terapéutico de un fármaco biosimilar del factor estimulante de colonias de granulocitos (G-CSF), zarzio, sobre la enfermedaddel hígado graso no alcohólico (NAFLD) en un modelo de rata. Treinta y dos ratas se dividieron aleatoriamente en cuatro grupos. Los grupos I y II fueron alimentados con una dieta estándar de laboratorio, mientras que los grupos III y IV fueron alimentados con una dieta alta en grasas (HFD) durante 14 semanas. Después de 12 semanas de alimentación, a los grupos I y III se les administró solución salina normal, y a los grupos II y IV se les administró zarzio por vía intraperitoneal (200 mg/kg/ día) durante dos semanas consecutivas. Se utilizó tinción de hematoxilina-eosina (H&E) para evaluar la morfología hepática y pancreática en todos los grupos, tinción con rojo aceite O (ORO) para la acumulación de lípidos, tinción de Masson para la fibrosis y ensayo de inmunohistoquímica para la expresión de la proteína hepática del sustrato 1 del receptor de insulina (IRS1), factor nuclear eritroide 2 relacionado con el factor 2 (Nrf2), factor de necrosis tumoral alfa (TNF-α) y caspasa-3 pancreática. Las ratas NAFLD (grupo III) desarrollaron esteatosis hepática con aumento de la acumulación de lípidos, fibrosis perisinusoidal, IRS1 y TNF-α regulados positivamente (todos P <0,05) sin un aumento significativo en la expresión de la proteína Nrf2 en comparación con el control normal. En comparación, las ratas modelo tratadas con zarzio (grupo IV) mostraron un rejuvenecimiento significativo de la arquitectura hepática, una reducción de la acumulación de grasa y fibrosis. Esto estuvo acompañado por la regulación positiva de Nrf2, la regulación negativa de la expresión de la proteína IRS1 y TNF-α (todas P <0,05). No se detectó correlación entre NAFLD y la enfermedad del páncreas graso no alcohólico (NAFPD). Sin embargo, las células β pancreáticas en el grupo III mostraron una mayor expresión de caspasa-3, que disminuyó (P <0,05) en el grupo IV. En conclusión, zarzio mejora la NAFLD al mejorar la capacidad antioxidante de las células hepáticas, reduciendo el IRS1 hepático, la expresión de la proteína TNF-α y la apoptosis de las células β pancreáticas, lo que sugiere que zarzio podría usarse como una terapia potencial para la NAFLD.
Assuntos
Animais , Masculino , Ratos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Medicamentos Biossimilares/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Imuno-Histoquímica , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Modelos Animais de Doenças , Células Secretoras de Insulina/efeitos dos fármacos , Fator 2 Relacionado a NF-E2 , Caspase 3 , Dieta Hiperlipídica/efeitos adversosRESUMO
Abstract While the role of cytokines in celiac disease has been investigated in detail, cytokine release in the event of the exposure of healthy subjects to glutens has only recently been studied. This study was aimed at determining the effects of corn and wheat glutens, incorporated as protein sources into the diet, on serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and the immunohistochemical distribution of CD3 and CD8 receptors in the small intestine in male rats. The study material comprised 24 twenty-day-old male Wistar albino rats, which were randomly assigned in equal numbers to three groups (2 rats/replicate and 4 replicates/group). The feed rations provided to all three groups contained high levels of proteins, which were soybean meal, corn gluten and wheat gluten in the control, corn and wheat groups, respectively. The in Control, Corn and Wheat groups serum IL-1 beta and TNF-alpha levels respectively 55.83 - 46.37; 81.65 - 61.95 and 81.65-61.31 was determined but these differences were statistically insignificant. Furthermore, immunohistochemical examination demonstrated a mathematical increase to have occurred in the distribution of the CD3 and CD8 receptors in the duodenum, jejunum and ileum samples of the corn and wheat groups. In result, based on the findings obtained in this study, we suggest that the long-term feeding of rats on high levels of gluten causes systemic adverse effects.
Assuntos
Animais , Ratos , Citocinas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Glutens/farmacologia , Imuno-Histoquímica , Ratos WistarRESUMO
Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.
Assuntos
Humanos , Feminino , Adulto , Fluoxetina/uso terapêutico , Fator de Necrose Tumoral alfa/sangue , Depressão/tratamento farmacológico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Feminina/psicologia , Antidepressivos/uso terapêutico , Hidrocortisona/sangue , Fertilização in vitro , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Resultado do Tratamento , Infertilidade Feminina/terapiaRESUMO
This aim of this study was to assess the molecular mechanism of osteoporosis in schizophrenia patients with risperidone use. Here, we investigated the effects of risperidone on cellular proliferation and apoptosis of a preosteoblast cell line, MC3T3-E1. Cell viability and apoptotic rate of MC3T3-E1 were detected by cell counting kit-8 and flow cytometry at a serial dose of risperidone and at different time points, respectively. Bone transformation relevant gene serum osteocalcin (BGP), collagen 1, tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) mRNA levels were determined by real-time PCR (qPCR). Their protein expression patterns were evaluated using western blot. The results revealed that risperidone dramatically inhibited MC3T3-E1 cell proliferation in a dose-dependent manner. It also significantly induced MC3T3-E1 cell apoptosis. TNF-α gene and protein levels were greatly enhanced after risperidone treatment. In contrast, BGP, collagen 1, OPG, and RANKL gene and protein levels were markedly downregulated. Our study indicated that risperidone suppressed MC3T3-E1 cell proliferation and induced apoptosis. It also regulated BGP gene and protein expression.
Assuntos
Animais , Osteoblastos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Risperidona/farmacologia , Proliferação de Células/efeitos dos fármacos , Osteocalcina/efeitos dos fármacos , Linhagem Celular , Colágeno/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/efeitos dos fármacos , Osteoprotegerina/efeitos dos fármacos , Citometria de FluxoRESUMO
SUMMARY: We sought to investigate the potential protective effect of Vitamin E supplementation against hepatocyte ultrastructural alterations induced by high fat diet (HFD) in a rat model of pre-diabetes. Therefore, rats were either fed with HFD (model group) or a standard laboratory chow (control group) for 12 weeks before being sacrificed. The protective group fed on a HFD and started the treatment with vitamin E (100 mg/kg/day, i.p) from day 1 until being sacrificed at week 12. The harvested liver tissues were examined using transmission electron microscopy (TEM) and blood samples were assayed for biomarkers of liver injury and prediabetes. TEM images showed that HFD induced profound pathological changes to the hepatocyte ultrastructure as demonstrated by degenerated hepatocytes with damaged cytoplasm that have mitochondrial swelling, dilation of endoplasmic reticulum, blebbing of plasma membranes, and cytoplasmic accumulations of lipid droplets and vacuoles, which were substantially but not completely protected with vitamin E. In addition, HFD significantly (p<0.05) augmented biomarkers of liver injury and pre-diabetes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C), which were significantly (p<0.05) reduced with vitamin E except TNF-α and TC. Furthermore, none of these biomarkers were reduced to the control level by vitamin E. We conclude that vitamin E is a partial protective agent against HFD-induced liver injury and pre-diabetes.
RESUMEN: El objetivo de este estudio fue investigar el posible efecto protector de la administración de suplementos de vitamina E contra las alteraciones ultraestructurales de los hepatocitos inducidas por una dieta rica en grasas (DRG) en un modelo de prediabetes en ratas. Antes de ser sacrificadas las ratas fueron alimentadas con DRG (grupo modelo) o un alimento estándar de laboratorio (grupo control) durante 12 semanas. El grupo protector se alimentó con una DRG y comenzó el tratamiento con vitamina E (100 mg/kg/día, i.p) desde el día 1 hasta sacrificarlo en la semana 12. Los tejidos hepáticos recolectados se examinaron mediante microscopía electrónica de transmisión (MET) y se tomaron muestras de sangre y se analizaron los biomarcadores de daño hepático y prediabetes. Las imágenes de MET mostraron que el DRG indujo cambios patológicos profundos en la ultraestructura de los hepatocitos, como lo demuestran los hepatocitos degenerados con citoplasma dañado e hinchazón mitocondrial, dilatación del retículo endoplasmático, formación de ampollas en las membranas plasmáticas y acumulaciones citoplásmicas de gotas de lípidos y vacuolas, los que fueron sustancialmente protegidas con vitamina E. Además, DRG aumentó significativamente (p <0,05) los biomarcadores de daño hepático y prediabetes como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), factor de necrosis tumoral alfa (TNF-α), malondialdehído (MDA), colesterol total (CT), triglicéridos (TG) y lipoproteína de colesterol de baja densidad (LDL-C), la cual se redujo significativamente (p <0,05) con vitamina E, excepto TNF-α y CT. Ninguno de estos biomarcadores se redujo al nivel de control por la vitamina E. Concluimos que la vitamina E es un agente protector parcial contra la lesión hepática inducida por DRG y la prediabetes.
Assuntos
Animais , Ratos , Estado Pré-Diabético/tratamento farmacológico , Vitamina E/administração & dosagem , Hepatócitos/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Aspartato Aminotransferases/efeitos dos fármacos , Vitamina E/farmacologia , Colesterol/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Hepatócitos/ultraestrutura , Microscopia Eletrônica de Transmissão , Alanina Transaminase/efeitos dos fármacos , Modelos Animais de Doenças , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fígado/efeitos dos fármacos , Malondialdeído/análiseRESUMO
Abstract AIMS The aim of the present study was to investigate the effects of combined training (CT) on total ghrelin and tumor necrosis factor-α (TNF-α) levels in obese middle-aged individuals. METHODS Twenty two obese middle-aged men (49.32 ± 5.74 years; Body mass index: 30.88 ± 1.64 kg/m²) were randomly assigned to a combined training group (CTG, n = 12) or a control group (CG, n = 10). The CT consisted of aerobic (50-85% of VO2peak) and resistance (6-10 RM) training performed three times per week, 60 min per session for 24 weeks. The anthropometric measurements, cardiorespiratory test (VO2peak), maximal strength assessment (1RM) and plasma concentrations of total ghrelin and TNF-α were determined before (Pre) and after 24 weeks (Post) of the experimental period. RESULTS Decreases were found in body fat percentage (Δ% -19.8) and waist circumference (Δ% -2.8) for CTG at the Post moment as compared to the Pre moment. In addition, the CTG demonstrated increases for VO2peak (Δ% 13.4) and for 1-RM of bench press (Δ% 78.1), leg press (Δ% 22.3) and arm curl (Δ% 19.3) at the Post moment as compared to the Pre moment. However, total ghrelin levels remained unchanged for CTG and CG after the experimental period, while TNF-α levels increased for CG (p ≤ 0.05). CONCLUSION the CT protocol performed was not effective in repairing total ghrelin levels and was not correlated with changes in the TNF-α; however, the exercise training was able to improve body composition and functional capabilities and contained the worsening of systemic inflammation associated to obesity.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Grelina/efeitos dos fármacos , Treino Aeróbico/instrumentação , Obesidade/fisiopatologia , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.
El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.
Assuntos
Animais , Feminino , Ratos , Anti-Inflamatórios/farmacologia , Síndrome do Ovário Policístico/metabolismo , Silimarina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Imuno-Histoquímica , Inflamação , Interleucina-6/metabolismo , Ratos Wistar , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Pseudobrickellia brasiliensis (Asteraceae) is a plant commonly known as arnica-do-campo and belongs to the native flora of the Brazilian Cerrado. The alcoholic extract of the plant has been used as an anti-inflammatory agent in folk medicine, but the biological mechanism of action has not been elucidated. The present study evaluated the composition of P. brasiliensis aqueous extract and its effects on pro-inflammatory cytokine production and lymphocyte proliferation. The extracts were prepared by sequential maceration of P. brasiliensis leaves in ethanol, ethyl acetate, and water. Extract cytotoxicity was evaluated by trypan blue exclusion assay, and apoptosis and necrosis were measured by staining with annexin V-FITC and propidium iodide. The ethanolic (ETA) and acetate (ACE) extracts showed cytotoxic effects. The aqueous extract (AQU) was not cytotoxic. Peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin and treated with AQU (100 μg/mL) showed reduced interferon (IFN)-γ and tumor necrosis factor (TNF)-α expression. AQU also inhibited lymphocyte proliferative response after nonspecific stimulation with phytohemagglutinin. The aqueous extract was analyzed by liquid chromatography coupled with photodiode array detection and mass spectrometry. Quinic acid and its derivatives 5-caffeoylquinic acid and 3,5-dicaffeoylquinic acid, as well as the flavonoids luteolin and luteolin dihexoside, were detected. All these compounds are known to exhibit anti-inflammatory activity. Taken together, these findings demonstrate that P. brasiliensis aqueous extract can inhibit the pro-inflammatory cytokine production and proliferative response of lymphocytes. These effects may be related to the presence of chemical substances with anti-inflammatory actions previously reported in scientific literature.
Assuntos
Humanos , Anti-Inflamatórios/farmacologia , Asteraceae/química , Proliferação de Células/efeitos dos fármacos , Interferon gama/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Interferon gama/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Extratos Vegetais/química , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.
Assuntos
Animais , Ratos , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Extratos Vegetais/farmacologia , Metotrexato/efeitos adversos , Hippophae/química , Antagonistas do Ácido Fólico/efeitos adversos , Estomatite/patologia , Língua/patologia , Vasos Sanguíneos/patologia , Extratos Vegetais/uso terapêutico , Expressão Gênica , Bochecha/patologia , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Resultado do Tratamento , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Lábio/patologia , Malondialdeído/análiseRESUMO
ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression.
Assuntos
Animais , Masculino , Triancinolona/farmacologia , Colágeno/análise , Fator de Necrose Tumoral alfa/análise , Úlceras Orais/tratamento farmacológico , Matricaria/química , Diabetes Mellitus Experimental/fisiopatologia , Anti-Inflamatórios/farmacologia , Fatores de Tempo , Cicatrização/efeitos dos fármacos , Imuno-Histoquímica , Extratos Vegetais/farmacologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Colágeno/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Resultado do Tratamento , Ratos Wistar , Úlceras Orais/patologia , Marcação In Situ das Extremidades Cortadas/métodos , AloxanoRESUMO
PURPOSE: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. METHODS: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1β, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1β and the VEGF immunostaining densities were also compared. RESULTS: Intraperitoneal ozone administration reversed TNF-α, IL-1β, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSION: Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.
Assuntos
Animais , Masculino , Ozônio/farmacologia , Peritonite/induzido quimicamente , Cicatrização/efeitos dos fármacos , Colo/cirurgia , Anastomose Cirúrgica , Distribuição Aleatória , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Ratos Wistar , Colo/patologia , Peroxidase/análise , Peroxidase/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Malondialdeído/análiseRESUMO
PURPOSE: To investigate the potential protective effect of allopurinol on reperfusion injury by determining the inflammatory response through the measurement of tumor necrosis factor-alpha (TNF-alpha). METHODS: Sixty rats were distributed into two groups: control and allopurinol and each group was divided into three subgroups, ischemia for two hours, ischemia for three hours and ischemia simulation. Allopurinol group rats received 100mg/kg dose of allopurinol, whereas control group rats received an equivalent dose of saline. Clamping of the infrarenal aorta was performed for two or three hours depending on the subgroup. Ischemia simulation subgroups did not suffer ischemia, just aortic dissection, and maintenance for three hours. After 72 hours of reperfusion, blood was collected by cardiac puncture for TNF-alpha measurement. RESULTS: Allopurinol reduced TNF-alpha significantly (p <0.001) when compared to the matching control subgroups (control X allopurinol in ischemia for two hours and for three hours). CONCLUSION: Allopurinol reduced the concentrations of serum TNF-alpha when used at different times of ischemia followed by reperfusion, which might indicate reduction of the inflammation provoked by the reperfusion injury.
Assuntos
Animais , Traumatismo por Reperfusão/metabolismo , Alopurinol/farmacologia , Cavidade Abdominal/irrigação sanguínea , Isquemia/cirurgia , Antimetabólitos/farmacologia , Fatores de Tempo , Traumatismo por Reperfusão/prevenção & controle , Distribuição Aleatória , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ratos Wistar , Modelos Animais , Inflamação/metabolismoRESUMO
T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.
Assuntos
Animais , Feminino , Humanos , Vacinas contra a AIDS/imunologia , Antígenos Virais/imunologia , /imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , HIV-1 , Imunidade Celular/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/administração & dosagem , /efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Sequência Conservada/imunologia , ELISPOT , Citometria de Fluxo , Vetores Genéticos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Infecções por HIV/prevenção & controle , Antígenos HLA-DR/imunologia , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , /metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos Endogâmicos BALB C , Plasmídeos , Ligação Proteica/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Human amnion mesenchymal cells (hAMCs), isolated from the amniotic membrane of human placenta, are a unique population of mesenchymal stem cells. Recent studies demonstrated that hAMCs could inhibit the activities and functions of several immune cells. However, their effect on inflammatory macrophages is largely unknown. This study investigated the effect of hAMCs on expression of inflammatory cytokines and mitogen-activated protein kinases (MAPKs)/NF-kB pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). RESULTS: The levels of TNF-α and IL-1ß secreted by LPS- stimulated THP-1 cells were increased significantly compared with those in the control group. After co-culture with different numbers of hAMCs, the levels of TNF-α and IL-1ß in LPS-stimulated THP-1 cells were significantly reduced compared with the LPS group. The mRNA expression of TNF-α and IL-1ß were also markedly inhibited. Moreover, treating LPS-stimulated THP-1 cells with hAMCs supernatants could also suppress TNF-α and IL-1ß production in THP-1 cells. Important signaling pathways involved in the production of TNF-α and IL-1ß were affected by hAMCs co-culture: hAMCs remarkably suppressed NF-kB activation and down-regulated the phosphorylation of ERK and JNK in LPS- stimulated THP-1 cells. CONCLUSIONS: Human amnion mesenchymal cells inhibited the production of TNF-α and IL-1ß secreted by LPS-stimulated THP-1 cells, partly through the suppression of NF-kB activation and ERK and JNK phosphorylation.
Assuntos
Humanos , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Interleucina-1beta/biossíntese , Células-Tronco Mesenquimais/fisiologia , Âmnio/citologia , Macrófagos/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacosRESUMO
OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. .
Assuntos
Animais , Masculino , Inibidores de Ciclo-Oxigenase/farmacologia , Hipocampo/efeitos dos fármacos , Indometacina/farmacologia , Monocinas/efeitos dos fármacos , Receptores da Bradicinina/efeitos dos fármacos , Estado Epiléptico/tratamento farmacológico , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Monocinas/análise , Pilocarpina , Ratos Wistar , Receptor B1 da Bradicinina/análise , Receptor B1 da Bradicinina/efeitos dos fármacos , /análise , /efeitos dos fármacos , Receptores da Bradicinina/análise , Estado Epiléptico/induzido quimicamente , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...
Assuntos
Animais , Humanos , Masculino , Ratos , Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Zingiberaceae/química , Análise de Variância , Inibidores da Angiogênese/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Interleucina-1/análise , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , /efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
Introduction. Rheumatoid arthritis patients under treatment with anti-TNF-α are at a high risk of developing active tuberculosis, and therefore, screening for latent tuberculosis infection is recommended before anti-TNF-α therapy. Objective. To compare the tuberculin test and IFNγ production induced by culture filtrate proteins(CFPs) and Mycobacterium tuberculosis-specific CFP-10 antigens in rheumatoid arthritis patients. Materials and methods. An analytic transversal study was conducted in rheumatoid arthritis patients treated at Hospital Universitario San Vicente Fundación between January and December 2007. IFNγ production in response to CFPs and CFP-10 was measured in the supernatants of whole blood cultures and evaluated for correlations with tuberculin reactivity. The degree of concordance between both tests was also established. Results. Forty-five patients were included, of which 14 (31.1%) had a tuberculin reaction of ≥10 mm of induration, 9 (20%) produced IFNγ in response to CFP-10, and 7 were positive for both tests. The correlation between tests was r=0.53 (IC 95%:0.28-0.72), and the global concordance between tests was80%, with a Kappa coefficient of 0.48 (IC95%:0.20-0.76). Conclusions. Only two tuberculin (-)/CFP-10+ "anergic" patients were observed. By contrast, six tuberculin +/CFP-10(-) "tuberculin false-positive" patients were observed. These data suggest that the tuberculin test is not an appropriate tool for determining the need for tuberculosis prophylaxis.
Introducción. Los pacientes con artritis reumatoide bajo tratamiento con anti-TNFα están en alto riesgo de desarrollar tuberculosis activa, por lo cual se recomienda hacer la tamización para infección latente de tuberculosis, antes de iniciar el tratamiento. Objetivo. Comparar la prueba de tuberculina y la producción de IFNγ inducida por antígenos CFP (Culture Filtrate Protein) y antígenos específicos de Mycobacterium tuberculosis (CFP-10) para el diagnóstico de infección latente de tuberculosis en pacientes con artritis reumatoide. Materiales y métodos. Se llevó a cabo un estudio transversal analítico en pacientes con artritis reumatoide atendidos en el Hospital Universitario San Vicente Fundación, entre enero y diciembre de 2007, a los cuales se les determinó la producción de IFNγ en respuesta a CFP y CFP-10 en sobrenadantes de cultivos de sangre total, y se correlacionó con la reacción en la prueba de tuberculina. Además, se estableció el grado de concordancia entre ambas pruebas. Resultados. Se incluyeron 45 pacientes, de los cuales, 14 (31,1 %) tuvieron un diámetro de induración ≥10 mm (tuberculina positiva), nueve (20 %) produjeron IFNγ en respuesta a CFP-10, y siete fueron positivos para ambas pruebas. La correlación entre las pruebas fue de r=0,53 (IC95%: 0,28-0,72) y la concordancia global entre pruebas fue de 80 %, con un coeficiente kappa de 0,48 (IC95%: 0,20-0,76). Conclusiones. Solo se observaron dos pacientes con tuberculina positiva y CFP-10 positivo "anérgicos" y se encontraron seis pacientes con tuberculina positiva y CFP-10 negativa "falsos positivos para tuberculina", lo cual sugiere que la prueba de la tuberculina no es la más adecuada para indicar profilaxis para tuberculosis.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos de Bactérias/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Teste Tuberculínico , Tuberculose/sangue , Tuberculose/diagnóstico , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Artrite Reumatoide/complicações , Células Cultivadas , Colômbia , Estudos Transversais , Tuberculose/complicaçõesRESUMO
PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.
OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.