RESUMO
This study investigated the effects of the alga lectin Hypnea cervicornis agglutinin (HCA) on rat zymosan-induced arthritis (ZyA). Zymosan (50-500 µg/25 µL) or sterile saline (Sham) was injected into the tibio-tarsal joint of female Wistar rats (180-200 g). Arthritic animals received morphine (4 mg/kg, intraperitoneal), indomethacin (5 mg/kg, intraperitoneal), or 2% lidocaine (100 µL, subcutaneous). HCA (0.3-3 mg/kg) was administered by intravenous route 30 min before or 2 h after zymosan. 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ, 4 µg, intra-articular) was given 30 min prior HCA. Hypernociception was measured every hour until 6 h, time in which animals were sacrificed for evaluation of leukocytes of the intra articular fluid and gene expression of TNF-α, IL-1, IL-10, and iNOS in the joint tissues using PCR techniques. Hypernociception was responsive to morphine and indomethacin, and its threshold was not altered by lidocaine. The post-treatment of HCA reduced both hypernociception and leukocyte influx. This antinociceptive effect was abolished either by ODQ and glibenclamide. HCA also reduced gene expression of iNOS and TNF-α. In conclusion, the antinociceptive effect of HCA in ZyA involves cyclic GMP signalization and selective modulation of cytokine expression.
Assuntos
Artrite/tratamento farmacológico , GMP Cíclico/metabolismo , Citocinas/biossíntese , Lectinas/uso terapêutico , Rodófitas , Zimosan/toxicidade , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Artrite/induzido quimicamente , Artrite/metabolismo , Expressão Gênica , Lectinas/isolamento & purificação , Lectinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant-induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid-reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.
Assuntos
Antioxidantes/metabolismo , Artrite/tratamento farmacológico , Artrite/metabolismo , Quercetina/farmacologia , Animais , Catalase/metabolismo , Ensaio Cometa , Dano ao DNA , Modelos Animais de Doenças , Feminino , Adjuvante de Freund , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Linfócitos/citologia , Mutagênicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
BACKGROUND: Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. PURPOSE: Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. STUDY DESIGN AND METHODS: This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. RESULTS: The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. CONCLUSION: Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.
Assuntos
Artrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Terpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite/metabolismo , Artrite/fisiopatologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular/métodos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
As low-level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low-level laser therapy (LLLT) on arthritis-induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm-2 ; LLLT at 30 Jcm-2 . Cytokine measurements by enzyme-linked immunosorbent assay and mRNA cytokine relative levels by real-time quantitative polymerase chain reaction were performed with arthritic ankle (IL-1ß, IL-6, TNF-α, IL-10 and TGF-ß). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4+ , CD8+ , Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+ population enrichment were observed in LLLT at 3 and 30 Jcm-2 groups, respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm-2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation.
Assuntos
Artrite/imunologia , Artrite/terapia , Terapia com Luz de Baixa Intensidade , Imunidade Adaptativa/efeitos da radiação , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/efeitos da radiação , Artrite/metabolismo , Artrite/patologia , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Temporomandibular joint (TMJ) is frequently involved with rheumatoid arthritis with a high prevalence that could result in a chronic pain state. Once the disease is established in the joint, the antigen-specific immune reaction initiates a neuro-immune cascade of events that causes sensitization of the central nervous system. This study establishes animal experimental models that evaluate the chronicity of albumin-induced arthritis hypernociception in the TMJ. Antigen-induced arthritis was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund's. Intra-articular injection of mBSA (10⯵g/TMJ/week) during 3â¯weeks resulted in a persistent inflammatory hypernociception which was characterized by an inflammatory episode characterized by the increased of lymphocytes, macrophages and pro-inflammatory interleukins IL-12 and IL-18. The persistent model of inflammatory hypernociception induced by arthritis in the TMJ elicited protein levels of P2X7 receptors, cathepsin S and fractalkine in the trigeminal subnucleus caudalis. Overall, the results of the present work suggest that a persistent inflammatory hypernociception of albumin-induced arthritis in the TMJ leads to the activation of the central nervous system signaling by P2X7/cathepsin S/fractalkine pathway.
Assuntos
Artrite/metabolismo , Catepsinas/metabolismo , Quimiocina CX3CL1/metabolismo , Nociceptividade , Receptores Purinérgicos P2X7/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Núcleos do Trigêmeo/metabolismo , Animais , Artrite/complicações , Artrite/imunologia , Artrite Experimental/induzido quimicamente , Modelos Animais de Doenças , Masculino , Ratos Wistar , Soroalbumina Bovina/administração & dosagem , Transdução de Sinais , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/imunologia , Núcleos do Trigêmeo/imunologiaRESUMO
The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67-89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin-(4ß â 8)-epicatechin-(4ß â 8, 2ß â O â 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1ß, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen.
Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Polímeros , Proantocianidinas/farmacologia , Sapindaceae/química , Animais , Anti-Inflamatórios/química , Artrite/tratamento farmacológico , Artrite/metabolismo , Artrite/patologia , Citocinas/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Feminino , Mediadores da Inflamação/metabolismo , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Proantocianidinas/químicaRESUMO
OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice. METHODS: Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA. RESULTS: Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1ß in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet. CONCLUSIONS: We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations.
Assuntos
Tecido Adiposo/metabolismo , Adiposidade , Artrite/metabolismo , Dieta , Inflamação/metabolismo , Lipodistrofia/metabolismo , Obesidade/metabolismo , Adipócitos , Adiponectina/sangue , Tecido Adiposo/patologia , Animais , Artrite/induzido quimicamente , Artrite/complicações , Artrite/patologia , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/metabolismo , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Suplementos Nutricionais , Inflamação/induzido quimicamente , Interleucina-1beta/sangue , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Leptina/sangue , Ácidos Linoleicos Conjugados/farmacologia , Metabolismo dos Lipídeos , Lipodistrofia/complicações , Masculino , Metaboloma , Camundongos Endogâmicos BALB C , Neutrófilos/metabolismo , Obesidade/complicações , Peroxidase/sangue , Soroalbumina BovinaRESUMO
The baroreflex is a critical physiological mechanism controlling cardiovascular function by modulating both the sympathetic and parasympathetic activities. Here, we report that electrical activation of the baroreflex attenuates joint inflammation in experimental arthritis induced by the administration of zymosan into the femorotibial cavity. Baroreflex activation combined with lumbar sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy dissected the mechanisms involved in the inflammatory modulation, highlighting the role played by sympathetic inhibition in the attenuation of joint inflammation. From the immunological standpoint, baroreflex activation attenuates neutrophil migration and the synovial levels of inflammatory cytokines including TNF, IL-1ß and IL-6, but does not affect the levels of the anti-inflammatory cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the inhibition of the sympathetic drive to the knee. These results reveal a novel physiological neuronal network controlling peripheral local inflammation.
Assuntos
Artrite/fisiopatologia , Barorreflexo , Inflamação/fisiopatologia , Articulação do Joelho/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adrenalectomia , Animais , Artrite/induzido quimicamente , Artrite/metabolismo , Modelos Animais de Doenças , Estimulação Elétrica , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Articulação do Joelho/patologia , Masculino , Neutrófilos/metabolismo , Ratos , Ratos Wistar , Esplenectomia , Vagotomia , ZimosanRESUMO
Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.
Assuntos
Lúpus Eritematoso Sistêmico/metabolismo , alfa-MSH/metabolismo , Animais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Artrite/tratamento farmacológico , Artrite/etiologia , Artrite/imunologia , Artrite/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Terpenos/efeitos adversos , alfa-MSH/administração & dosagemRESUMO
The aim of this study was to evaluate the effect of low-level laser therapy on acute zymosan-induced arthritis, with respect to the laser action on inflammatory cells influx, release of pro-inflammatory mediators, metalloproteinases activity into the joint cavity and the cartilage repair process. Arthritis was induced in male Wistar rats (250-280 g) by intra-articular injection of zymosan (1 mg dissolved in 50 µl of a sterile saline solution) into one rear knee joint. Animals were irradiated immediately, 1 and 2 h after zymosan administration with a semiconductor laser InGaAIP (660 nm, 10 mW, 2.5 J/cm(2), 10 s). In the positive control group, animals were injected with the anti-inflammatory drug dexamethasone 1 h prior to the zymosan administration. Treatment with laser significantly inhibited leukocytes influx, the release of IL-1 and IL-6 and also the activity of metalloproteinase-2 and 9, into the joint cavity. In conclusion, laser therapy was effective in reducing inflammation to sites of injury and inhibit activation of proteases (gelatinase) suggesting less degradation of collagen tissue in experimental model of acute arthritis.