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INTRODUCTION: Aerobic physical training (APT) reduces eosinophilic airway inflammation, but its effects and mechanisms in severe asthma remain unknown. METHODS: An in vitro study employing key cells involved in the pathogenesis of severe asthma, such as freshly isolated human eosinophils, neutrophils, and bronchial epithelial cell lineage (BEAS-2B) and lung fibroblasts (MRC-5 cells), was conducted. Additionally, an in vivo study using male C57Bl/6 mice, including Control (Co; n = 10), Trained (Exe; n = 10), house dust mite (HDM; n = 10), and HDM + Trained (HDM + Exe; n = 10) groups, was carried out, with APT performed at moderate intensity, 5x/week, for 4 weeks. RESULTS: HDM and bradykinin, either alone or in combination, induced hyperactivation in human neutrophils, eosinophils, BEAS-2B, and MRC-5 cells. In contrast, IL-10, the primary anti-inflammatory molecule released during APT, inhibited these inflammatory effects, as evidenced by the suppression of numerous cytokines and reduced mRNA expression of the B1 receptor and ACE-2. The in vivo study demonstrated that APT decreased bronchoalveolar lavage levels of bradykinin, IL-1ß, IL-4, IL-5, IL-17, IL-33, TNF-α, and IL-13, while increasing levels of IL-10, klotho, and IL-1RA. APT reduced the accumulation of polymorphonuclear cells, lymphocytes, and macrophages in the peribronchial space, as well as collagen fiber accumulation, epithelial thickness, and mucus accumulation. Furthermore, APT lowered the expression of the B1 receptor and ACE-2 in lung tissue and reduced bradykinin levels in the lung tissue homogenate compared to the HDM group. It also improved airway resistance, tissue resistance, and tissue damping. On a systemic level, APT reduced total leukocytes, eosinophils, neutrophils, basophils, lymphocytes, and monocytes in the blood, as well as plasma levels of IL-1ß, IL-4, IL-5, IL-17, TNF-α, and IL-33, while elevating the levels of IL-10 and IL-1RA. CONCLUSION: These findings indicate that APT inhibits the severe asthma phenotype by targeting kinin signaling.
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Asma , Bradicinina , Humanos , Animais , Camundongos , Masculino , Interleucina-10 , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-17 , Interleucina-33 , Interleucina-4 , Interleucina-5 , Fator de Necrose Tumoral alfaRESUMO
Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.
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Citocinas , Leucemia , Fitoterapia , Humanos , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Leucemia/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Several benefits of aerobic training for asthmatic patients have been demonstrated. However, its effects on systemic inflammation and on airway remodeling mediators and lung mechanics are unknown. This prospective study included 21 intermittent and mild asthma patients, and as primary outcomes, the evaluation of pro- and anti-inflammatory and pro- and antifibrotic mediators in exhaled breath condensate (EBC) and blood were performed, beyond the cell counting in blood and in induced sputum. Aerobic training was performed for 3 months, 3 times per week. Aerobic training increased the levels of anti-inflammatory cytokines and of antifibrotic mediators in the breath condensate: IL-1ra (p = 0.0488), IL-10 (p = 0.0048), relaxin-3 (p = 0.0019), and klotho (p < 0.0043), respectively. Similarly, in plasma, increased levels of IL-1ra (p = 0.0147), IL-10 (p < 0.0001), relaxin-3 (p = 0.004), and klotho (p = 0.0023) were found. On contrary, reduced levels of proinflammatory cytokines in the breath condensate, IL-1ß (p = 0.0008), IL-4 (p = 0.0481), IL-5 (p < 0.0001), IL-6 (p = 0.0032), IL-13 (p = 0.0013), and TNF-α (p = 0.0001) and profibrotic markers VEGF (p = 0.0017) and TSLP (p = 0.0056) were found. Similarly, in plasma, aerobic training significantly reduced the levels of proinflammatory cytokines IL-1ß (p = 0.0008), IL-4 (p = 0.0104), IL-5 (p = 0.0001), IL-6 (p = 0.006), IL-13 (p = 0.0341), and TNF-α (p = 0.0003) and of profibrotic markers VEGF (p = 0.0009) and TSLP (p < 0.0076). Fractional exhaled nitric oxide (FeNO) was reduced after the intervention (p = 0.0313). Regarding inflammatory cells in sputum, there was a reduction in total cells (p = 0.008), eosinophils (p = 0.009), and macrophages (p = 0.020), as well as of blood eosinophils (p = 0.0203) and lymphocytes (p = 0.0198). Aerobic training positively modulates chronic airway inflammation and remodeling mediators, beyond to improve systemic inflammation in intermittent and mild asthmatic patients.
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Asma , Relaxina , Humanos , Expiração , Testes Respiratórios , Interleucina-13 , Interleucina-10 , Proteína Antagonista do Receptor de Interleucina 1 , Fator de Necrose Tumoral alfa , Interleucina-6 , Interleucina-4 , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular , Interleucina-5 , Óxido Nítrico , Asma/terapia , Citocinas , Inflamação , PulmãoRESUMO
Background: Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. Methods: We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese (n = 12), overweight (n = 17), and obese grade I (n = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. Result: CPE improved forced vital capacity (FVC) % (p < 0.001) and peak expiratory flow (PEF) % (p < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese (p < 0.01), overweight (p < 0.0009), and obese (p < 0.0001) groups; resistance of distal airways (R5Hz-R20Hz) in non-obese (p < 0.01), overweight (p < 0.0012), and obese (p < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese (p < 0.01), overweight (p < 0.0006), and obese (p < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; central resistance (RCentral) in non-obese (p < 0.01), overweight (p < 0.001), and obese (p < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese (p < 0.03), overweight (p < 0.001), and obese (p < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight (p < 0.0094) and obese groups (p < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese (p < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight (p < 0.03) and obese (p < 0.0001) groups. Conclusion: CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.
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Stroke is the main cause of death and functional disability. The available therapy affects only 5% of patients, and new therapeutic approaches have been constantly tested. Transcranial photobiomodulation (PBM) is promising for its neuroprotective effect on brain injuries. Thus, the present study investigated the PBM effects in an in vivo model of ischemic stroke induced by photothrombosis (PT). Five different groups of Wistar rats were submitted or not to a daily dose of fish oil or/and laser sessions for 2 months. The ischemia volume was evaluated by stereology; GFAP, Iba and NeuN by immunohistochemistry; TNF-α, IL-1ß, IL-6, IL-10 and TGF-ß by ELISA assay. PBM influenced both the lesion volume and the GFAP. Furthermore, PBM and Ω-3 or both reduced Iba RNAm. PBM reduced TNF-α, IL-1ß, IL-6, brain damage, neuroinflammation and microglial activation, and it increased astroglial activity in peri-lesioned region after stroke.
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Terapia com Luz de Baixa Intensidade , Acidente Vascular Cerebral , Animais , Infarto Encefálico , Humanos , Microglia , Ratos , Ratos Wistar , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.
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Lesões Encefálicas , Epilepsia , Acidente Vascular Cerebral , Animais , Epilepsia/etiologia , Ratos , Ratos Wistar , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic inflammatory disease with a poor prognosis and very few available treatment options. Low-level laser therapy (LLLT) has been gaining prominence as a new and effective anti-inflammatory and immunomodulatory agent. Can lung inflammation and the airway remodeling be regulated by LLLT in an experimental model of IPF in C57Bl/6 mice? The present study investigated if laser attenuates cellular migration to the lungs, the airway remodeling as well as pro-fibrotic cytokines secretion from type II pneumocytes and fibroblasts. Mice were irradiated (780 nm and 30 mW) and then euthanized fifteen days after bleomycin-induced lung fibrosis. Lung inflammation and airway remodeling were evaluated through leukocyte counting in bronchoalveolar lavage fluid (BALF) and analysis of collagen in lung, respectively. Inflammatory cells in blood were also measured. For in vitro assays, bleomycin-activated fibroblasts and type II pneumocytes were irradiated with laser. The pro- and anti-inflammatory cytokines level in BALF as well as cells supernatant were measured by ELISA, and the TGFß in lung was evaluated by flow cytometry. Lung histology was used to analyze collagen fibers around the airways. LLLT reduced both migration of inflammatory cells and deposition of collagen fibers in the lungs. In addition, LLLT downregulated pro-inflammatory cytokines and upregulated the IL-10 secretion from fibroblasts and pneumocytes. Laser therapy greatly reduced total lung TGFß. Systemically, LLLT also reduced the inflammatory cells counted in blood. There is no statistical difference in inflammatory parameters studied between mice of the basal group and the laser-treated mice. Data obtained indicate that laser effectively attenuates the lung inflammation, and the airway remodeling in experimental pulmonary fibrosis is driven to restore the balance between the pro- and anti-inflammatory cytokines in lung and inhibit the pro-fibrotic cytokines secretion from fibroblasts.
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Remodelação das Vias Aéreas , Citocinas/metabolismo , Fibrose Pulmonar Idiopática/radioterapia , Lasers , Animais , Líquido da Lavagem Broncoalveolar/química , Células Cultivadas , Citocinas/análise , Modelos Animais de Doenças , Regulação para Baixo/efeitos da radiação , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Fibrose Pulmonar Idiopática/patologia , Terapia a Laser , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima/efeitos da radiaçãoRESUMO
When conservative treatments fail, hip osteoarthritis (OA), a chronic degenerative disease characterized by cartilage wear, progressive joint deformity, and loss of function, can result in the need for a total hip arthroplasty (THA). Surgical procedures induced tissue trauma and incite an immune response. Photobiomodulation therapy (PBMt) using low-level laser therapy (LLLT) and/or light-emitting diode therapy (LEDT) has proven effective in tissue repair by modulating the inflammatory process and promoting pain relief. Therefore, the aim of this study was to analyze the immediate effect of PBMt on inflammation and pain of patients undergoing total hip arthroplasty. The study consisted of 18 post-surgical hip arthroplasty patients divided into two groups (n = 9 each) placebo and active PBMt who received one of the treatments in a period from 8 to 12 h following THA surgery. PBMt (active or placebo) was applied using a device consisting of nine diodes (one super-pulsed laser of 905 nm, four infrared LEDs of 875 nm, and four red LEDs 640 nm, 40.3 J per point) applied to 5 points along the incision. Visual analog scale (VAS) and blood samples for analysis of the levels of the cytokines TNF-α, IL-6, and IL-8 were recorded before and after PBMt application. The values for the visual analog scale as well as those in the analysis of TNF-α and IL-8 serum levels decreased in the active PBMt group compared to placebo-control group (p < 0.05). No decrease was observed for IL-6 levels. We conclude that PBMt is effective in decreasing pain intensity and post-surgery inflammation in patients receiving total hip arthroplasty.
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Dor Aguda/radioterapia , Artroplastia de Quadril/efeitos adversos , Inflamação/radioterapia , Terapia com Luz de Baixa Intensidade , Idoso , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , Medição da Dor , Placebos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were preincubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1ß, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1ß, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1ß, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.
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Interleucina-10/imunologia , Estresse Oxidativo , Condicionamento Físico Animal , Pneumonia/imunologia , Síndrome do Desconforto Respiratório/imunologia , Lesão Pulmonar Aguda , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/sangue , Citocinas/imunologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-10/farmacologia , Lipopolissacarídeos , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Pneumonia/induzido quimicamente , Síndrome do Desconforto Respiratório/induzido quimicamenteRESUMO
This study evaluated the role of the phototherapy and exercise training (EXT) as well as the combined treatment in general symptoms, pain, and quality of life in women suffering from fibromyalgia (FM). A total of 160 women were enrolled and measures were carried out in two sets: it was sought to identify the acute effect for a single phototherapy and EXT session (Set 1); long-term effect (10 weeks) of the interventions (Set 2). Phototherapy irradiation was performed at 11 locations in their bodies, employing a cluster with nine diodes (one super-pulsed infrared 905 nm, four light-emitting diodes [LEDs] of 640 nm, and four LEDs of 875 nm, 39.3 J per location). Algometry and VAS instrument were applied to evaluate pain. The FM symptoms were evaluated with Fibromyalgia Impact Questionnaire (FIQ) and Research Diagnostic Criteria (RDC) instruments. Quality of life was assessed through SF-36 survey. Set 1: pain threshold was improved with the phototherapy, and EXT improved the pain threshold for temporomandibular joint (right and left body side) and occipital site (right body side). Set 2: there was improved pain threshold in several tender points with the phototherapy and EXT. There was an overlap of therapies to reduce the tender point numbers, anxiety, depression, fatigue, sleep, and difficulty sleeping on FIQ/RDC scores. Moreover, quality of life was improved with both therapies. The phototherapy and EXT improved the pain threshold in FM women. A more substantial effect was noticed for the combined therapy, in which pain relief was accomplished by improving VAS and FIQ scores as well as quality of life.
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Terapia por Exercício , Fibromialgia/radioterapia , Terapia com Luz de Baixa Intensidade , Adulto , Terapia Combinada , Feminino , Humanos , Medição da Dor , Limiar da Dor , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.
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This study investigates the effect of photobiomodulation therapy (PBMT) on collagen type I and III, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF) in experimentally induced tendinopathy in female aged rats. Tendinopathy was induced by the Achilles tendoncollagenase peritendinous. Forty-two Wistar rats (Norvegicus albinus) were used; groups consisted of 36 aged animals (18 months old; mean body weight, 517.7 ± 27.54 g) and 6 adult animals (12 weeks old; mean body weight, 266± 19.30 g). The animals were divided into three groups: control, aged tendinopathy, and aged tendinopathy PBMT; the aged groups were subdivided based on time to euthanasia: 7, 14, and 21 days. PBMT involved a gallium-arsenide-aluminum laser (Theralaser, DMC®) with active medium operating at wavelength 830 ± 10 nm, 50 mW power, 0.028 cm2 laser beam, 107 J/cm2 energy density, 1.8 W/cm2 power density, and an energy of 3 J per point. The laser was applied by direct contact with the left Achilles tendon during 60 s per point at a frequency of three times per week, until the euthanasia date (7, 14, and 21 days). VEGF, MMP-3, and MMP-9 were analyzed by immunohistochemistry, and collagen type I and III by Sirius red. PBMT increased the deposition of collagen type I and III in a gradual manner, with significant differences relative to the group aged tendonitis (p < 0.001), and in relation to VEGF (p < 0.001); decreased expression of MMP-3 and 9 were observed in group aged tendinopathy (p < 0.001). PBMT, therefore, increased the production of collagen type I and III, downregulated the expression of MMP-3 and MMP-9, and upregulated that of VEGF, with age and age-induced hormonal deficiency.
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Colágeno Tipo II/efeitos da radiação , Colágeno Tipo I/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Metaloproteinase 9 da Matriz/efeitos da radiação , Tendinopatia/radioterapia , Fator A de Crescimento do Endotélio Vascular/efeitos da radiação , Tendão do Calcâneo , Animais , Modelos Animais de Doenças , Feminino , Lasers Semicondutores/uso terapêutico , Metaloproteinase 3 da Matriz/efeitos da radiação , Ratos , Ratos WistarRESUMO
PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. METHODS: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI·kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min·d, 5 d·wk for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1ß, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor ß levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. RESULTS: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1ß (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P < 0.001), and transforming growth factor ß (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. CONCLUSIONS: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.
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Condicionamento Físico Animal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/terapia , Serotonina/metabolismo , Transdução de Sinais , Animais , Bleomicina , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Teste de Esforço , Masculino , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismoRESUMO
BACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage. This study evaluated the effects of Cr supplementation in a model of lung I/R. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response. RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleukin-1ß (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized. Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and anti-oxidant properties of Cr and modulation of TLRs.
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Creatina/administração & dosagem , Isquemia/tratamento farmacológico , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antioxidantes , Apoptose/efeitos dos fármacos , Western Blotting , Suplementos Nutricionais , Imuno-Histoquímica , Inflamação/prevenção & controle , Fator de Crescimento Insulin-Like I/análise , Pulmão/efeitos dos fármacos , Masculino , Óxido Nítrico/análise , Ratos , Ratos Wistar , Receptores Toll-Like/análiseRESUMO
The aim of this experimental study was to investigate the effects of low-intensity light-emitting diode (LED) phototherapy on the inflammatory process in the calcaneal tendon of ovariectomized rats (OVX) through the involvement of the inflammatory mediators interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Thirty-five female Wistar rats were divided into 4 groups: 3 groups of OVX rats totaling 30 rats (untreated OVX rats [OVX injury group], treated OVX rats [OVX LED group], and control OVX rats; subgroups existed based on the sampling times, which were 3, 7, and 14 days) and 1 group of non-OVX rats (not OVX; n = 5). Tendon injury was induced by trauma using a 208-g mass placed at 20 cm from the right tendon of each animal with energy of 0.70 J. The animals were treated 12 h after tendonitis with LED therapy and every 48 h thereafter until euthanasia (at 3, 7, or 14 days). The tendons were dissected and stored in liquid nitrogen at -196 °C, thawed only at the time of immunoenzymatic testing (ELISA). Groups treated with LED showed a decrease in the number of pro-inflammatory cells, IL-6, and TNF-α (p <0.05), and an increase in IL-10 (p < 0.05) when compared to the not OVX group (p < 0.05). It was concluded that low-intensity LED treatment using the parameters and wavelength of 945 nm in the time periods studied reduced the release of IL-6 and TNF-α and increased the release of IL-10, thereby improving the inflammatory response in OVX rats.
Assuntos
Tendão do Calcâneo/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Ovariectomia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/metabolismo , Animais , Citocinas/metabolismo , Feminino , Inflamação/metabolismo , Inflamação/terapia , Ratos , Ratos WistarRESUMO
This study was designed to determine if the levels of oxidative stress markers are influenced by low-level laser therapy (LLLT) in mdx mice subjected to high-intensity exercise training on an electric treadmill. We used 21 C57BL/10ScSn-Dmdmdx/J mice and 7 C57BL/10ScSn mice, all aged 4 weeks. The mice were divided into four groups: a positive control group of normal, wild-type mice (WT); a negative control group of untreated mdx mice; a group of mdx mice that underwent forced high-intensity exercise on a treadmill (mdx fatigue); and another group of mdx mice with the same characteristics that were treated with LLLT at a single point on the gastrocnemius muscle of the hind paw and underwent forced high-intensity exercise on a treadmill. The mdx mice treated with LLLT showed significantly lower levels of creatine kinase (CK) and oxidative stress than mdx mice that underwent forced high-intensity exercise on a treadmill. The activities of the antioxidant enzyme superoxide dismutase (SOD) were higher in control mdx mice than in WT mice. LLLT also significantly reduced the level of this marker. LLLT had a beneficial effect also on the skeletal muscle performance of mdx mice. However, the single application of LLLT and the dose parameters used in this study were not able to change the morphology of a dystrophic muscle.
Assuntos
Biomarcadores/metabolismo , Terapia com Luz de Baixa Intensidade/métodos , Fadiga Muscular/fisiologia , Estresse Oxidativo , Condicionamento Físico Animal , Animais , Creatina Quinase/sangue , Teste de Esforço , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Carbonilação Proteica , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Fibromyalgia (FM) is a syndrome most prevalent in women, in whom it is characterized mainly by chronic pain. An important issue is that many patients with FM are reported to have temporomandibular dysfunction (TMD), and the coexistence of these pathologies generates a clinical outcome of high complexity. The literature is unclear regarding an effective therapy for reducing pain in patients with both comorbidities. Exercise training and phototherapy (low-level laser therapy with light-emitting diode) are two of the approaches used to treat pain. Thus, the aim of this study is to assess the potential role of exercise training plus phototherapy in reducing chronic pain in women with FM and TMD. A further aim is to determine whether the interventions can improve quality of life and modulate endogenous serotonin. METHODS/DESIGN: A randomized controlled clinical trial will be conducted. It will involve 60 women ≥ 35 years of age with a diagnosis of FM and TMD. After recruitment, patients will be randomly allocated to one of four groups: a control group (no intervention), a group that will receive a phototherapy intervention (PHO), a group that will be prescribed muscle-stretching, aerobic, and facial exercises (EXT), or a group that will receive phototherapy plus exercise interventions (PHO + EXT). The trial will last 10 weeks, and the following outcomes will be evaluated on two separate occasions (baseline and within 24 h after the last day of the protocol). Pain intensity will be analyzed using a visual analogue scale and the McGill Pain Questionnaire, and pain thresholds will be punctuated using a digital algometer. FM symptoms will be assessed using the Fibromyalgia Impact Questionnaire, and quality of life will be determined with the 36-item Short Form Health Survey. Serotonin levels will be evaluated in salivary samples using a competitive enzyme-linked immunosorbent assay. DISCUSSION: This is the first randomized controlled trial in which the role of phototherapy, exercise training, and a combination of these interventions will be evaluated for chronic pain in patients with FM and TMD. The results will offer valuable clinical evidence for objective assessment of the potential benefits and risks of procedures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02279225. Registered 27 October 2014.
Assuntos
Terapia por Exercício , Fibromialgia/terapia , Terapia com Luz de Baixa Intensidade , Transtornos da Articulação Temporomandibular/terapia , Adulto , Biomarcadores/metabolismo , Brasil , Protocolos Clínicos , Terapia Combinada , Desenho de Equipamento , Terapia por Exercício/efeitos adversos , Feminino , Fibromialgia/diagnóstico , Fibromialgia/metabolismo , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Humanos , Lasers Semicondutores , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/instrumentação , Medição da Dor , Qualidade de Vida , Projetos de Pesquisa , Saliva/metabolismo , Serotonina/metabolismo , Inquéritos e Questionários , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/psicologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Freezing changes sperm integrity remarkably. Cryopreservation involves cooling, freezing, and thawing and all these contribute to structural damage in sperm, resulting in reduced fertility potential. Low-level laser irradiation (LLLI) could increase energy supply to the cell and cause reactive oxygen species reduction (ROS), contributing to the restoration of oxygen consumption and adenosine triphosphate synthesis (ATP) in the mitochondria. Our goal was to analyze the effects of low-level laser irradiation on sperm motility and integrity of the plasma membrane and acrosome in cryopreserved bovine sperm. STUDY DESIGN/MATERIALS AND METHODS: We analyzed 09 samples of bull semen (Bos taurus indicus), divided into three groups: a control group without laser irradiation, a 4J group subjected to a laser irradiation dose of 4 joules, and a 6J group subjected to dose of 6 joules. Samples were divided for the analysis of cell viability and acrosomal membrane integrity using flow cytometry; another portion was used for motion analysis. Irradiation was performed in petri dishes of 30 mm containing 3 ml of semen by an aluminum gallium indium phosphide laser diode with a wavelength of 660 nm, 30 mW power, and energy of 4 and 6 joules for 80 and 120 seconds respectively. Subsequently, the irradiated and control semen samples were subjected to cryopreservation and analyzed by flow cytometry (7AAD and FITC-PSA) using the ISAS--Integrated Semen Analysis System. RESULTS: Flow cytometry showed an increase in the percentage of live sperm cells and acrosome integrity in relation to control cells when subjected to irradiation of low-power laser in two different doses of 4 and 6 joules (p < 0.05). In the analysis of straightness, percentage of cell movement, and motility, a dose of 4 joules was more effective (p < 0.05). CONCLUSION: We conclude that LLLI may exert beneficial effects in the preservation of live sperm. A dose of 4 joules prior to cryopreservation was more effective than a dose of 6 joules in preserving sperm motility.
Assuntos
Acrossomo/metabolismo , Membrana Celular/metabolismo , Criopreservação , Lasers , Preservação do Sêmen , Motilidade dos Espermatozoides/efeitos da radiação , Animais , Bovinos , Sobrevivência Celular/efeitos da radiação , Citometria de Fluxo , MasculinoRESUMO
[Purpose] The aim of the present study was to evaluate the effect of a biteplate on the cranio-cervical posture of children with bruxism. [Subjects and Methods] Twelve male and female children aged six to 10â years with a diagnosis of bruxism participated in this study. The children used a biteplate during sleep for 30 days and were submitted to three postural evaluations: initial, immediately following placement of the biteplate, and at the end of treatment. Posture analysis was performed with the aid of the Alcimagem(®) 2.1 program. Data analysis (IBM SPSS Statistics 2.0) involved descriptive statistics and the Student's t-test. [Results] A statistically significant difference was found between the initial cranio-cervical angle and the angle immediately following placement of the biteplate. However, no statistically significant difference was found between the initial angle and the angle after one month of biteplate usage. [Conclusion] No significant change in the cranio-cervical posture of the children was found one month of biteplate usage. However, a reduction occurred in the cranio-cervical angle when the biteplate was in position.
RESUMO
The wound-healing process plays an essential role in the protective response to epidermal injury by tissue regeneration. In the elderly, skin functions deteriorate as a consequence of morphological and structural changes. This study aimed to evaluate and compare the effect of low-level laser therapy (LLLT) in cutaneous wound healing in young and aged rats. A total of 60 male rats comprising 30 young (± 30 days) and 30 aged (± 500 days) was used. The animals were divided into four experimental groups and underwent skin wound and/or treatment with LLLT (660 nm, 30 mW, 1.07 W/cm(2), 0.028 cm(2), 72 J/cm(2), and 2 J). Analyses were conducted to verify the effects of LLLT in the tissue repair process, in the gene expression, and protein expression of TNF-α, IL-1ß, and IL-10, obtained in skin wound model. Results showed that there were significant differences between the young control group and the aged control group and their respective treated groups (LLLT young and LLLT aged). We conclude that LLLT has shown to be effective in the treatment of skin wounds in young and aged animals at different stages of the tissue repair process, which suggests that different LLLT dosimetry should be considered in treatment of subjects of different ages. Further clinical trials are needed to confirm these findings in clinical settings.