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Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
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BACKGROUND: Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. METHODS: Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMß5, PMSß6, PSMß7, PSMß8, PSMß9, and PSMß10), and protein (PSMß1, PSMß5, PSMß1i, PSMß5i) expression of proteasome subunits. RESULTS: Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMß8 and PSMß9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSß6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMß5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMß5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit ß1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). CONCLUSIONS: The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMß8 and PSMß9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.
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Antirreumáticos , Artrite Experimental , Masculino , Humanos , Camundongos , Animais , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Metotrexato/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Músculo Esquelético , Inflamação/tratamento farmacológicoRESUMO
OBJECTIVE: This study aimed to evaluate whether ligature-induced periodontitis and rheumatoid arthritis (RA) potentiate the deleterious effects on functional capacity, periodontal and synovial tissues, leukocyte migration, and interleukin 17 (IL-17) levels, and to investigate the repercussions of single Freund's Complete Adjuvant (FCA) injection associated with periodontitis. MATERIALS AND METHODS: Fifty-one male Wistar rats were randomised into six groups: control (CG, n = 8), RA (RAG, n = 9), periodontitis (PG, n = 9), periodontitis and RA (PRAG, n = 9), periodontitis and intradermal injection (PIDG, n = 9), and periodontitis and intra-articular injection (PIAG, n = 7). The animals underwent ligature placement and one or two injections with FCA to induce RA. Motor disability, nociceptive threshold, joint edema, and muscle strength were assessed, and the animals were euthanized on day 30. Synovial fluid, hemimandibles, and knee joints were collected. RESULTS: PRAG showed no reduction of edema or improvement of muscle strength, whereas it showed most significant changes in leukocyte migration, morphological analyses of the synovial membrane (SM), and radiographic and histometric analyses of the jaw. The PIAG showed some alterations, though not permanent. CONCLUSION: Ligature-induced periodontitis and RA induced by two FCA injections accentuated the deleterious effects on functional capacity, leukocyte migration, synovial and periodontal tissues.
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Artrite Reumatoide , Periodontite , Animais , Masculino , Ratos , Artrite Reumatoide/complicações , Edema/induzido quimicamente , Leucócitos , Modelos Teóricos , Periodontite/complicações , Ratos Wistar , Movimento Celular , Interleucina-17RESUMO
Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.
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Gout arthritis commonly affects joint regions by deposition of crystals, promoting functional damage mainly during periods of exacerbation. Cryotherapy is a commonly used resource to contain inflammatory processes, however, its use during a gout crisis is not yet well understood. Therefore, the objective was to evaluate the parameters of Wistar rats submitted to an experimental gout model and treated with dual cryotherapy protocol. Twenty-one male Wistar rats were used, separated into three groups: control group (CG), lesion group (LG), and lesion + cryotherapy group (LCG). Gout model induction was through intra-articular injection, with urate crystal solution, in the right knee and cryoimmersion treatment was performed for 20 minutes at a temperature of 5° ± 2°C. Seven evaluations and two treatment moments were performed, and the following parameters were analyzed: joint edema, grip strength, joint disability, motor function, and leukocyte migration through synovial lavage. In the statistical analysis we used SPSS 20.0 with Generalized Linear Models, with least significant difference posttest, always with 5% significance level. The treatment reduced edema, promoted strength recovery, and was effective in reducing total leukocytes in the synovial fluid. No difference was observed between the injured groups for joint disability and motor function. Cryotherapy promoted edema reduction and increased pelvic limb grip strength in Wistar rats during the acute period.
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Gota , Hipotermia Induzida , Animais , Crioterapia , Gota/patologia , Gota/terapia , Inflamação , Masculino , Ratos , Ratos WistarRESUMO
Arthritis can be defined as a painful musculoskeletal disorder that affects the joints. Hesperidin methyl chalcone (HMC) is a flavonoid with analgesic, anti-inflammatory, and antioxidant effects. However, its effects on a specific cell type and in the zymosan-induced inflammation are unknown. We aimed at evaluating the effects of HMC in a zymosan-induced arthritis model. A dose-response curve of HMC (10, 30, or 100 mg/kg) was performed to determine the most effective analgesic dose after intra-articular zymosan stimuli. Knee joint oedema was determined using a calliper. Leukocyte recruitment was performed by cell counting on knee joint wash as well as histopathological analysis. Oxidative stress was measured by colorimetric assays (GSH, FRAP, ABTS and NBT) and RT-qPCR (gp91phox and HO-1 mRNA expression) performed. In vitro, oxidative stress was assessed by DCFDA assay using RAW 264.7 macrophages. Cytokine production was evaluated in vivo and in vitro by ELISA. In vitro NF-κB activation was analysed by immunofluorescence. We observed HMC reduced mechanical hypersensitivity and knee joint oedema, leukocyte recruitment, and pro-inflammatory cytokine levels. We also observed a reduction in zymosan-induced oxidative stress as per increase in total antioxidant capacity and reduction in gp91phox and increase in HO-1 mRNA expression. Accordingly, total ROS production and macrophage NFκB activation were diminished. HMC interaction with NFκB p65 at Ser276 was revealed using molecular docking analysis. Thus, data presented in this work suggest the usefulness of HMC as an analgesic and anti-inflammatory in a zymosan-induced arthritis model, possibly by targeting NFκB activation in macrophages.
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Artralgia/tratamento farmacológico , Chalconas/farmacologia , Hesperidina/análogos & derivados , Inflamação/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Zimosan/farmacologia , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/fisiologia , Artralgia/induzido quimicamente , Artralgia/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Hesperidina/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular/métodos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacosRESUMO
This study investigated the repercussions of adjuvant-induced arthritis (AIA) on body composition and the structural organization of the soleus and cardiac muscles, including their vascularization, at different times of disease manifestation. Male rats were submitted to AIA induction by intradermal administration of 100 μL of Mycobacterium tuberculosis (50 mg/mL), in the right hind paw. Animals submitted to AIA were studied 4 (AIA4), 15 (AIA15), and 40 (AIA40) days after AIA induction as well as a control group of animals not submitted to AIA. Unlike the control animals, AIA animals did not gain body mass throughout the evolution of the disease. AIA reduced food consumption, but only on the 40th day after induction. In the soleus muscle, AIA reduced the wet mass in a time-dependent manner but increased the capillary density by the 15th day and the fiber density by both 15 and 40 days after induction. The diameter of the soleus fiber decreased from the 4th day after AIA induction as well as the capillary/fiber ratio, which was most evident on the 40th day. Moreover, AIA induced slight histopathological changes in the cardiac muscle that were more evident on the 15th day after induction. In conclusion, AIA-induced changes in body composition as well as in the soleus muscle fibers and vasculature have early onset but are more evident by the 15th day after induction. Moreover, the heart may be a target organ of AIA, although less sensitive than skeletal muscles.
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Animais , Masculino , Ratos , Artrite Experimental/patologia , Composição Corporal , Músculo Esquelético/patologia , Miocárdio/patologia , Artrite Experimental/metabolismo , Músculo Esquelético/metabolismo , Modelos Animais de Doenças , Miocárdio/metabolismoRESUMO
Background: Gout is the most common inflammatory arthritis worldwide. It is a painful inflammatory disease induced by the deposition of monosodium urate (MSU) crystals in the joints and peri-articular tissues. Sesquiterpene lactones (SLs) are secondary metabolite biosynthesized mainly by species from the family Asteraceae. It has been demonstrated that SLs present anti-inflammatory, analgesic, antitumoral, antiparasitic, and antimicrobial activities. In this study, we aimed at evaluating the efficacy of the SL budlein A in a model of acute gout arthritis in mice. Methods: Experiments were conducted in male Swiss or male LysM-eGFP mice. Animals were treated with budlein A (1 or 10 mg/kg) or vehicle 30 min before stimulus with MSU (100 µg/10 µL, intra-articular). Knee joint withdrawal threshold and edema were evaluated using electronic von Frey and caliper, respectively, 1-15 h after MSU injection. Leukocyte recruitment was determined by counting cells (Neubauer chamber), H&E staining, and using LysM-eGFP mice by confocal microscopy. Inflammasome components, Il-1ß, and Tnf-α mRNA expression were determined by RT-qPCR. IL-1ß and TNF-α production (in vitro) and NF-κB activation (in vitro and in vivo) were evaluated by ELISA. In vitro analysis using LPS-primed bone marrow-derived macrophages (BMDMs) was performed 5 h after stimulation with MSU crystals. For these experiments, BMDMs were either treated or pre-treated with budlein A at concentrations of 1, 3, or 10 µg/mL. Results: We demonstrated that budlein A reduced mechanical hypersensitivity and knee joint edema. Moreover, it reduced neutrophil recruitment, phagocytosis of MSU crystals by neutrophils, and Il-1ß and Tnf-α mRNA expression in the knee joint. In vitro, budlein A decreased TNF-α production, which might be related to the inhibition of NF-κB activation. Furthermore, budlein A also reduced the IL-1ß maturation, possibly by targeting inflammasome assembly in macrophages. Conclusion: Budlein A reduced pain and inflammation in a model of acute gout arthritis in mice. Therefore, it is likely that molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as budlein A, are interesting approaches to treat gout flares.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by debilitating pain, cartilage destruction, and loss of joint function. Management of RA includes drugs that target NF-κB and downstream cytokine production. Therefore, molecules that act by inhibiting this signaling pathway without the severe side effects of, for instance, corticoids would be suitable therapeutic strategies. Budlein A is a sesquiterpene lactone with antinociceptive and anti-inflammatory properties related to the inhibition of pro-inflammatory cytokines and neutrophil recruitment. In this study, the effect of budlein A was evaluated in antigen-induced arthritis (AIA) in mice. At the 26th day, leukocyte recruitment to the knee joint, knee contents of proteoglycans, blood levels of ALT and AST, stomach tissue myeloperoxidase activity, and RT-qPCR for pro-inflammatory gene mRNA expression in knee joint samples was performed. NF-κB luciferase activity was evaluated in RAW 264.7 macrophages. Budlein A treatment dose-dependently inhibited AIA-induced mechanical hyperalgesia, edema, total leukocytes and neutrophil recruitment, and proteoglycan degradation. Budlein A did not induce gastric or liver damage. Budlein also inhibited AIA-induced Il-33, Tnf, Il-1ß, preproET-1, and Cox-2 mRNA expression. In vitro, budlein reduced TNF- and IL-1ß-induced NF-κB activity in RAW 264.7 macrophages. Altogether, we demonstrate that budlein A ameliorates AIA-induced inflammation and pain by targeting NF-κB. Importantly, budlein A does not induce in vivo side effects, suggesting that it possesses a favorable pre-clinical profile as analgesic and it is a prosperous molecule to be further investigated for the treatment of RA.
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Artrite Experimental/tratamento farmacológico , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Antígenos/efeitos adversos , Artrite Experimental/induzido quimicamente , Citocinas/efeitos dos fármacos , Inflamação/prevenção & controle , Camundongos , NF-kappa B/antagonistas & inibidores , Dor/prevenção & controle , Células RAW 264.7RESUMO
Vitamin D (VitD) is a hormone primarily synthesized in human skin under the stimulation of ultraviolet radiation. Beyond its endocrine role in bone metabolism, VitD is endowed with remarkable immunomodulatory properties. The effects of VitD on the immune system include the enhancement of microbicidal ability of monocytes/macrophages and the down-modulation of inflammatory cytokines produced by T lymphocytes. VitD deficiency is involved in many health problems, including immune-mediated diseases such as autoimmune disorders. Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease that compromises the joints, causing cartilage destruction and bone erosion. RA treatment usually consists of combined therapies that generally suppress the entire immune response leading to increased susceptibility to infections. This review describes the main effects of VitD on innate and adaptive immune system and also VitD status in inflammatory rheumatic diseases such as RA. Despite some controversies, the majority of reports reinforce the idea that lower VitD levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. Therefore, supplementation with VitD to achieve normal serum levels is worthwhile as an aforethought. Original data concerning the potential applicability of 1,25-dihydroxyvitamin D3 (VitD3), the active form of vitamin D, as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3 associated with proteoglycan (PG), which is a specific cartilage antigen, was tested in the course of experimental arthritis. This association significantly lowered clinical scores and local histopathological alterations. Even though local analysis of T cell subsets and cytokine production did not reveal any difference between the experimental groups, VitD3+PG association significantly reduced cytokine production by spleen cells. These results suggest that VitD3 played a role as a tolerogenic adjuvant by down-modulating the course of experimental RA. Considering this tolerogenic effect of VitD3+PG association, further investigations will reveal its plausible use in human RA.
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Anti-Inflamatórios/metabolismo , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/metabolismo , Imunidade Adaptativa , Animais , Artrite Experimental/terapia , Artrite Reumatoide/terapia , Autoimunidade , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Humanos , Tolerância Imunológica , Imunidade Inata , Imunomodulação , Inflamação , Proteoglicanas/metabolismo , Vitamina D/uso terapêutico , Deficiência de Vitamina D/terapiaRESUMO
Rheumatoid arthritis (RA) may promote endothelial dysfunction. This phenomenon requires further investigation, especially in collagen-induced arthritis (CIA), as it is considered the experimental model most similar to RA. The objectives of this study were to identify CIA-induced changes in noradrenaline (NE) and acetylcholine (ACh) responses in mice aortas that may suggest endothelial dysfunction in these animals. Moreover, we characterize CIA-induced modifications in inducible nitric oxide synthase (iNOS) expression in the aortas and cardiac and renal tissues taken from these mice that may be related to possible endothelial dysfunction. Male DBA/1J mice were immunized with 100 µg of emulsified bovine collagen type II (CII) plus complete Freund's adjuvant. Twenty-one days later, these animals received a boost of an additional 100 µg plus incomplete Freund's adjuvant. Fifteen days after the onset of the disease, aortic rings from CIA and control mice were challenged with NE and ACh in an organ bath. In these animals, iNOS was detected through immunohistochemical analysis of aorta, heart and kidneys. Plasma nitrite concentration was determined using the Griess reaction. CIA did not change NE or ACh responses in mice aorta but apparently increased the iNOS expression not only in aorta, but also in cardiac and renal microcirculation. In parallel, CIA reduced nitrite plasma concentration. In mice, CIA appears to increase the presence of iNOS in aorta, as well as in heart and in kidney microcirculation. This iNOS increase occurs apparently in parallel to a reduction of the bioavailability of NO. This phenomenon does not appear to change NE or ACh responses in aorta.
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Aorta/enzimologia , Artrite Experimental/enzimologia , Óxido Nítrico Sintase Tipo II/genética , Acetilcolina/farmacologia , Animais , Aorta/fisiopatologia , Artrite Experimental/fisiopatologia , Artrite Reumatoide/enzimologia , Artrite Reumatoide/fisiopatologia , Disponibilidade Biológica , Bovinos , Colágeno Tipo II , Circulação Coronária , Endotélio/fisiopatologia , Adjuvante de Freund , Rim/irrigação sanguínea , Rim/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Microcirculação , Nitritos/sangue , Norepinefrina/química , Norepinefrina/farmacologiaRESUMO
Atualmente no mercado se encontra o extrato de óleo insaponificável de abacate e soja, considerado potente anti-inflamatório, agente antioxidante e analgésico, eficaz no tratamento de distúrbios que afetam os tecidos conjuntivos. O objetivo desse estudo foi avaliar a eficácia deste medicamento no tratamento da doença periodontal induzida em ratos com artrite. Foram utilizados 60 ratos (Rattus Norvegicus) submetidos à indução de artrite por antígeno (AIA) e a indução da doença periodontal (DP) através da inserção de ligadura no segundo molar superior. Após a remoção das ligaduras, em todos os dentes foi realizada raspagem radicular (R). Os animais foram distribuídos randomicamente em 4 grupos, avaliados em três períodos experimentais (7, 15 e 30 dias). Grupo Controle (CTR); Grupo ASU; Grupo ASU e artrite (ASU/AR); Grupo AR. Após os períodos experimentais pós-tratamento, suas maxilas e articulação da pata dianteira foram removidos para processamento laboratorial. A porcentagem de volume ósseo nas regiões proximais foi analisada por microtomografia (MicroCT). Não houve diferenças entre os grupos, entretanto foi verificado na análise intragrupos que no grupo ASU/AR houve um aumento estatisticamente significativo na porcentagem óssea no período de 30 dias em relação ao período de 7 dias e no grupo AR um aumento na porcentagem óssea no período de 30 dias em comparação ao período de 15 dias. Os períodos avaliados apresentaram leve infiltrado inflamatório, desorganização das fibras colágenas e integridade do cemento radicular. Dessa forma conclui-se que o ASU não adicionou efeito ao reparo periodontal após tratamento da periodontite induzida associada ou não a indução de artrite experimental em ratos.
The avocado/soybean unsaponifiables(ASU) is a drug that has been used for the treatment of rheumatoid arthritis(AR) and other connective tissue disorders due to their potent anti-inflammatory and analgesic effect and antioxidant. Thus, the aim of this study was to evaluate the effect of this drug on the treatment of the ligatureinduced periodontitis in rats with experimental arthritis. Sixty rats were used in this experiment. The arthritis was induced in thirty rats by injection of specific antigen (AIA) and the periodontitis was induced in all the rats by a insertion of a cotton ligature in the periodontal sulcus of the second upper molar. The ligatures removal and the scaling was performed 7 days after the ligatures placement. The animals were randomly divided in four groups: Control (CTR), ASU, ASU/AR and AR. The animals were euthanized 7, 15 and 30 days after the treatments. The maxilla's and the joint of the front paw was removed to perform the analysis. The percentage of bone tissue in the proximal were analyzed by the micro CT. No statistical differences were detected between the groups. Regarding the intragroup analysis it was showed an enhance on the bone volume in the ASU/AR at 30 days compared with the period of 7 days, and an improve in bone volume the AR at 30 days compared with the period of 15 days. The descriptive histology showed that all the groups presented a mild inflammatory infiltrate, disorganization of collagen fibers and cementum integrity. In conclusion, the consumption of the ASU did not add any additional effect on the periodontal healing after the treatment of the ligature-induced periodontitis in rats with/without experimental arthritis
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Animais , Ratos , Glycine max , Tecido Conjuntivo , Persea , Artrite Experimental , Fitoterapia , Periodontite , Doenças Periodontais , Análise de Variância , Analgésicos , Anti-Inflamatórios , AntioxidantesRESUMO
The mechanisms of muscle wasting and decreased mobility have a major functional effect in rheumatoid arthritis, but they have been poorly studied. The objective of our study is to describe muscular involvement and the pathways in an experimental model of arthritis compared to the pathways in disuse atrophy. Female Wistar rats were separated into three groups: control (CO), collagen-induced arthritis (CIA), and immobilized (IM). Spontaneous locomotion and weight were evaluated weekly. The gastrocnemius muscle was evaluated by histology and immunoblotting to measure the expression of myostatin (a negative regulator), LC3 (autophagy), MuRF-1 (proteasome-mediated proteolysis), MyoD, and myogenin (satellite-cell activation). The significance level was set at P < 0.05, and histological analysis of joints confirmed the severity of the arthropathy. There was a significant difference in spontaneous locomotion in the CIA group. Animal body weight, gastrocnemius muscle weight, and relative muscle weight decreased 20%, 30%, and 20%, respectively, in the CIA rats. Inflammatory infiltration and swelling were present in the gastrocnemius muscles of the CIA rats. The mean cross-sectional area was reduced by 30% in the CIA group and by 60% in the IM group. The expressions of myostatin and LC3 between the groups were similar. There was increased expression of MuRF-1 in the IM (1.9-fold) and CIA (3.1-fold) groups and of myogenin in the muscles of the CIA animals (1.7-fold), while MyoD expression was decreased in the IM (20%) rats. This study demonstrated that the development of experimental arthritis is associated with decreased mobility, body weight, and muscle loss. Both IM and CIA animal models presented muscle atrophy, but while proteolysis and the regeneration pathways were activated in the CIA model, there was no activation of regeneration in the IM model. We can assume that muscle atrophy in experimental arthritis is associated with the disease itself and not simply with decreased mobility.