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Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.
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Fibromialgia , Hiperalgesia , Ratos , Feminino , Animais , Hiperalgesia/tratamento farmacológico , Fibromialgia/complicações , Fibromialgia/tratamento farmacológico , Fibromialgia/patologia , Adrenalectomia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Solução Salina/farmacologiaRESUMO
OBJECTIVE AND DESIGN: Biochanin A (BCA), a phytoestrogen, has various pharmacological properties. This study was conducted to compare BCA's therapeutic property against 17-ß estradiol replacement therapy in zymosan-induced arthritis (ZIA) in mice. Additionally, we further investigated in vitro the anti-inflammatory action on neutrophils. TREATMENT: Ovariectomized (OVX) and non-OVX mice were pretreated with BCA (1, 3 and 9 mg/kg) or estrogen (50 µg/kg) for 14 days prior to ZIA. Neutrophils were pretreated with BCA (1, 10 and 100 µM) for 1 h prior to phorbol 12-myristate 13-acetate. METHODS: Anti-inflammatory effects of BCA were evaluated by cellular infiltrate, paw edema and cytokine measurement. In vitro, apoptosis was assessed by morphology and flow cytometry. Neutrophil extracellular traps (NET) were determined by fluorescent microscopy and DNA release. Statistical differences were determined by one- or two-way ANOVA. RESULTS: BCA inhibited neutrophil accumulation, paw edema and proinflammatory cytokine (TNF-α and IFN-γ) and increased anti-inflammatory cytokines (IL-4 and IL-10) in OVX and non-OVX mice, similar to 17-ß estradiol replacement therapy. In vitro, BCA increased apoptosis and consequently reduced NETs. CONCLUSION: BCA has a notable anti-inflammatory effect, similar to 17-ß estradiol, and is especially effective for treatment of ZIA. These results suggest that BCA may be promising for the treatment of postmenopausal arthritis.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/tratamento farmacológico , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Genisteína/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Artrite/induzido quimicamente , Citocinas/metabolismo , DNA/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Camundongos , Neutrófilos/efeitos dos fármacos , Ovariectomia , Acetato de Tetradecanoilforbol , ZimosanRESUMO
To determine the effectiveness of low-level phototherapy (i.e. light-emitting diode therapy [LEDtherapy] or light amplification by stimulated emission of radiation therapy [LASERtherapy]) on pain, skeletal muscle injury (creatine kinase [CK] levels and edema) and skeletal muscle function (range of movement and strength) in people undergoing an exercise protocol. (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PEDro, SciELO and LILACS up to May 2014), we included randomized controlled trials, quasi-randomized controlled trials and crossover studies in which study participants were allocated to receive either low-level phototherapy or placebo treatment. Phototherapy should have been applied in a single treatment session, either before or after an exercise protocol. We identified 15 studies involving 317 participants. Meta-analyses were limited by substantial heterogeneity. Compared to the placebo group, reduction in CK levels was only observed when LASERtherapy was applied before an exercise protocol (standardized mean difference = -0.66; 95 % CI = -1.30, -0.02). No between-group difference in edema, range of movement and strength were detected when phototherapy was applied before or after exercise. Evidence from this review suggests that low-level phototherapy may not have substantial effect in the treatment of skeletal muscle injury and pain caused by exercise. Definitive conclusions are limited due to the small number of included studies in each meta-analysis, disparities across the included studies and small sample sizes.
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Mialgia/terapia , Fototerapia/métodos , Exercício Físico/fisiologia , Humanos , Mialgia/fisiopatologia , Resultado do TratamentoRESUMO
The aim of this study was to evaluate the effectiveness of pre-exercise low-level phototherapy (Light-Emitting Diode therapy [LEDtherapy] or Light Amplification by Stimulate Emission of Radiation therapy [LASERtherapy]) in increasing exercise capacity and muscle performance of people undergoing exercise when compared to placebo treatment. Randomized controlled trials and crossover studies were sought on CENTRAL, MEDLINE, EMBASE, SciELO, PEDro and LILACS from its inception up to February 2015. References lists of included studies were sought for additional relevant research. Two authors independently extracted data on study design, treatment parameters, exercise capacity (number of repetitions, time to exhaustion, blood lactate concentration and lactate dehydrogenase activity) and muscle performance (torque, power and strength) using an structured table. Agreement should be reached by consensus or by a third reviewer. Sixteen studies involving 297 participants were included. Improvement of number of repetitions (mean difference [MD] [95 % confidence interval] = 3.51 repetitions [0.65-6.37]; P = 0.02), delay in time to exhaustion (MD = 4.01 s [2.10-5.91]; P < 0.0001), reduction in lactate levels (MD = 0.34 mmol/L [0.19-0.48]; P < 0.00001) and increased peak torque (MD = 21.51 Nm [10.01-33.01]; P < 0.00001) were observed when LASERtherapy was applied. LEDtherapy meta-analyses were performed with two studies and retrieved no between-group statistically significant difference in power, lactate levels or time to exhaustion. Although our results suggest that LASERtherapy is effective in improving skeletal muscle exercise capacity, the quality of the current evidence is limited.
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Exercício Físico/fisiologia , Terapia com Luz de Baixa Intensidade/métodos , Músculo Esquelético/efeitos da radiação , Humanos , Ácido Láctico/sangue , Masculino , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
CONTEXT: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae). OBJECTIVE: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K⺠channel pathway. MATERIALS AND METHODS: We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 µl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E2 (PGE2; 100 ng/paw) or dopamine (DA; 30 µg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). RESULTS: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE2 test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE2 test. DISCUSSION AND CONCLUSION: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K⺠channel pathway.
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Aldeídos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Canais KATP/metabolismo , Monoterpenos/uso terapêutico , Óxido Nítrico/metabolismo , Dor Nociceptiva/prevenção & controle , Monoterpenos Acíclicos , Aldeídos/administração & dosagem , Aldeídos/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , GMP Cíclico/antagonistas & inibidores , Cymbopogon/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Glibureto/farmacologia , Indonésia , Canais KATP/antagonistas & inibidores , Masculino , Camundongos , Monoterpenos/administração & dosagem , Monoterpenos/antagonistas & inibidores , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Dor Nociceptiva/imunologia , Dor Nociceptiva/metabolismo , Óleos Voláteis/química , Limiar da Dor/efeitos dos fármacos , Óleos de Plantas/química , Bloqueadores dos Canais de Potássio/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Mesosphaerum pectinatum (L.) Kuntze (Lamiaceae), also known as sambacaitá, is a medicinal plant widely used in northeastern Brazil for the treatment of inflammatory and painful conditions, bacterial infections and cancer. Hence, the medicinal use of this species is quite meaningful to the search for bioactive compounds. AIM OF THE STUDY: To evaluate the antinociceptive and anti-inflammatory activities of the pectinolide-enriched fraction of Mesosphaerum pectinatum (PEF) in animal models. MATERIALS AND METHODS: The PEF was analyzed with HPLC-DAD and 1H and 13C NMR. After the analysis, compounds of the pectinolide class were detected as major constituents in this fraction. The PEF (50, 100 and 200 mg/kg, p.o.) and the reference drugs - morphine (3.0 mg/kg, p.o.) and dexamethasone (2.0 mg/kg, p.o.) - were evaluated using models for nociception (hot plate, formalin-induced licking response) or inflammation (carrageenan-induced peritonitis and ear edema model). RESULTS: The PEF significantly decreased the licking time of the animals treated when compared to the control group (second phase). In the carrageenan-induced peritonitis model, PEF (100 and 200 mg/kg) significantly decreased total and differential leukocyte counts. The PEF (0.3, 1.0 and 3.0 mg/ear) significantly reduced mice ear edema at the same extent and like the results obtained with the standard drug (dexamethasone). The MPO activity was reduced in mice ear at doses of 1 and 3 mg/ear. Antinociceptive effect on the hot plate test was not observed, demonstrating that there is no analgesic activity. CONCLUSION: Our results suggest that the pectinolide-enriched fraction exhibits anti-inflammatory effects and that it is involved with inhibiting the release of the inflammatory mediators.
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Lamiaceae , Peritonite , Camundongos , Animais , Carragenina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Edema/tratamento farmacológico , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Dexametasona/uso terapêuticoRESUMO
Introduction: Nephelium lappaceum L. (Sapindaceae) is a plant known as rambutan. It is used for various purposes in traditional medicine. Objective: We aimed to evaluate the antinociceptive effects of the ethanol extract of the fruit peel of N. lappaceum (EENL), the mechanisms involved in these effects, and the acute toxicity in zebrafish. Methods: We performed chromatography coupled to mass spectrometry, acute toxicity assay in zebrafish, and evaluation in mice submitted to models of nociception and locomotor activity. Results: We identified (epi)-catechin, procyanidin B, and ellagic acid and its derivatives in EENL. We did not find any toxicity in zebrafish embryos incubated with EENL. The locomotor activity of mice submitted to oral pretreatment with EENL was not changed, but it reduced the abdominal constrictions induced by acetic acid, the licking/biting time in both the first and second phase of formalin testing and capsaicin testing, and carrageenan-induced paw mechanical allodynia. Oral pretreatment with EENL increased latency time in the hot plate test. This antinociceptive effect was significantly reversed by naloxone, L-arginine, and glibenclamide respectively showing the participation of opioid receptors, nitric oxide, and KATP channels as mediators of EENL-induced antinociception. Conclusion: EENL causes antinociception with the participation of opioid receptors, nitric oxide, and KATP channels, and is not toxic to zebrafish.
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Although it has been previously demonstrated that oxytocin (OXT) receptor stimulation can control skeletal muscle mass in vivo, the intracellular mechanisms that mediate this effect are still poorly understood. Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. The results indicated that both OXT and WAY-267,464 suppressed muscle proteolysis, and this effect was blocked by the addition of ATB. Furthermore, the WAY-induced anti-catabolic action on protein metabolism did not involve the coupling between OXTR and Gαi since it was insensitive to pertussis toxin (PTX). The decrease in overall proteolysis induced by WAY was probably due to the inhibition of the autophagic/lysosomal system, as estimated by the decrease in LC3 (an autophagic/lysosomal marker), and was accompanied by an increase in the content of Ca2+-dependent protein kinase (PKC)-phosphorylated substrates, pSer473-Akt, and pSer256-FoxO1. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca2+ release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca2+-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis.
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Músculo Esquelético , Proteólise , Proteínas Proto-Oncogênicas c-akt , Receptores de Ocitocina , Animais , Ratos , Músculo Esquelético/metabolismo , Ocitocina/farmacologia , Ocitocina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Ocitocina/genética , Transdução de SinaisRESUMO
Introduction: Increases in fat mass and reductions in lean mass are associated with the frailty and mortality of older people. In this context, Functional Training (FT) is an option to increase lean mass and reduce fat mass in older people. Thus, this systematic review aims to investigate the effects of FT on body fat and lean mass in older people. Methods: We included randomized controlled clinical trials, with at least one intervention group that employed FT, with the age of participants ≥60 years; and participants physically independent and healthy. We performed the systematic investigation in Pubmed MEDLINE, Scopus, Web of Science, Cochrane Library, and Google Scholar. We extracted the information and used the PEDro Scale to assess the methodological quality of each study. Results: Our research found 3,056 references with five appropriate studies. Of the five studies, three presented reductions in fat mass, all of them with interventions between three and 6 months, different training dose parameters, and 100% of the sample was composed of women. On the other hand, two studies with interventions between 10 and 12 weeks presented conflicting results. Conclusion: Despite the limited literature about lean mass, it appears that long-term FT interventions may reduce fat mass in older women. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399257, identifier CRD42023399257.
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This study investigated the effects of functional (FT) and combined (CT) training on memory T cells and functional fitness of postmenopausal women. 108 participants were randomly allocated to the control (CG), FT and CT groups. Functional fitness was assessed through physical tests similar to daily activities, such as dressing on and taking off a t-shirt (DTTS), 10-meter walking and countermovement jump. The CCR7 and CD45RA surface markers were used to characterize the memory T cells. Regarding the frequency of memory T cells, both training protocols reduced the percentage of CD4+ Terminally Differentiated Effector Memory T Cells Re-Expressing CD45RA (TEMRA) (FT: -38.73 %, p = 0.0455; CT: -30.43 %, p = 0.0036) and CD8+ TEMRA cells (FT: -22.24 %, p < 0.0013; CT: -13.13 %, p = 0.0051). Also, both FT and CT increased the percentage of central memory (TCM) CD4+ (FT: +55.22 %, p = 0.0104; CT: +68.03 %, p = 0.0167) and CD8+ (FT: +142.00 %, p < 0.0001; CT: +83.76 %, p = 0.0001) T cells. Furthermore, FT and CT increased the percentages of CD8+ effector memory T cells (TEM) (FT: +63.58 %, p < 0.0001; CT: +14.12 %, p = 0.0041). Regarding functional fitness, both training protocols reduced the time required to perform the DTTS (FT: -19.71 %, p < 0.0001; CT: -14.69 %, p < 0.0001) and 10-m walk tests (FT: -13.05 %, p < 0.0001; CT: -12.83 %, p < 0.0001), in addition to improving jumping ability (FT: +29.97 %, p < 0.0001; CT: +20.00 %, p < 0.0001), both compared to the pre-test or to the CG. Therefore, both FT and CT seem to be equally effective alternatives for promoting the reduction of CD4+ and CD8+ TEMRA cells, increasing the frequency of TCM and TEM cells, and improving functional fitness of postmenopausal women.
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Memória Imunológica , Subpopulações de Linfócitos T , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Feminino , Humanos , Antígenos Comuns de Leucócito , Células T de Memória , Pós-MenopausaRESUMO
INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs widely used due to their pharmacological potential, demonstrating anti-inflammatory, analgesic, or antipyretic activity. However, prolonged use of these medications can lead to the development of gastric ulcers in patients. This review aimed to find patents for drugs with an anti-inflammatory and gastroprotective character to treat NSAID-induced gastric ulcers. AREAS COVERED: For the treatment of NSAID-induced gastric ulcers, formulations with different action mechanisms were found, including donors of nitric oxide, heterocyclic compounds, and natural products. EXPERT OPINION: Many of the structures found have already been used in clinic settings and others, and according to the results found, they are promising for the treatment of gastric ulcers.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antiulcerosos/farmacologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/farmacologia , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/farmacologia , Humanos , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/farmacologia , Patentes como Assunto , Úlcera Gástrica/induzido quimicamenteRESUMO
The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) ω3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19-75 years, randomized into placebo or supplemented (2.2 g of ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNFα, MCP1, IL1ß, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, ß-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through ω3 supplementation through binding to the GPR120 receptor. TRIAL REGISTRATION: ClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.
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Hepatopatia Gordurosa não Alcoólica , Estresse do Retículo Endoplasmático , Humanos , Inflamação , Leucócitos Mononucleares , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Sobrepeso , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Spinal cord injury (SCI) is a condition that affects the central nervous system, is characterized by motor and sensory impairments, and impacts individuals' lives. The objective of this study was to evaluate the effects of resistance training on oxidative stress and muscle damage in spinal cord injured rats. METHODOLOGY: Forty Wistar rats were selected and divided equally into five groups: Healthy Control (CON), Sham (SHAM) SCI Untrained group (SCI-U), SCI Trained group (SCI- T), SCI Active Trained group (SCI- AT). Animals in the trained groups were submitted to an incomplete SCI at T9. Thereafter, they performed a protocol of resistance training for four weeks. RESULTS: Significant differences in muscle damage markers and oxidative stress in the trained groups, mainly in SCI- AT, were found. On the other hand, SCI- U group presented higher levels of oxidative stress and biomarkers of LDH and AST. CONCLUSION: The results highlight that resistance training promoted a decrease in oxidative stress and a significative response in muscle damage markers.
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AIMS: Although it is well established that skeletal muscle contains oxytocin (OT) receptors and OT-knockout mice show premature development of sarcopenia, the role of OT in controlling skeletal muscle mass is still unknown. Therefore, the present work aimed to determine OT's effects on skeletal muscle protein metabolism. MAIN METHODS: Total proteolysis, proteolytic system activities and protein synthesis were assessed in isolated soleus muscle from prepubertal female rats. Through in vivo experiments, rats received 3-day OT treatment (3UI.kg-1.day-1, i.p.) or saline, and muscles were harvested for mass-gain assessment. KEY FINDINGS: In vitro OT receptor stimulation reduced total proteolysis, specifically through attenuation of the lysosomal and proteasomal proteolytic systems, and in parallel activated the Akt/FoxO1 signaling and suppressed atrogenes (e.g., MuRF-1 and atrogin-1) expression induced by motor denervation. On the other hand, the protein synthesis was not altered by in vitro treatment with the OT receptor-selective agonist. Although short-term OT treatment did not change the atrogene mRNA levels, the protein synthesis was stimulated, resulting in soleus mass gain, probably through an indirect effect. SIGNIFICANCE: Taken together, these data show for the first time that OT directly inhibits the proteolytic activities of the lysosomal and proteasomal systems in rat oxidative skeletal muscle by suppressing atrogene expression via stimulation of Akt/FoxO signaling. Moreover, the data obtained from in vivo experiments suggest OT's ability to control rat oxidative skeletal muscle mass.
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Anabolizantes/farmacologia , Lisossomos/metabolismo , Músculo Esquelético/metabolismo , Ocitocina/farmacologia , Biossíntese de Proteínas , Proteólise , Animais , Feminino , Lisossomos/efeitos dos fármacos , Lisossomos/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Estresse Oxidativo , Ocitócicos/farmacologia , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Treatment of temporomandibular disorders (TMD) is a challenge for health care professionals. Therefore, new approaches have been investigated, such as the use of natural products. Objective This systematic review aims to summarize the natural products used in treatment of experimental models of TMD. Methodology A systematic search was performed in the databases Medline, Web of Science, Scopus, Embase, SciELO, LILACS, and Scholar Google databases in January 2020, dating from their inception. Pre-clinical studies with natural products for intervention in experimental TMD were included. Two reviewers independently selected the studies, extracted the data, and evaluated the risk of bias. Results 17 records were selected, and 17 different natural products were found, including three lectins, three plants or algae extracts, three sulfated polysaccharides, three cocoa preparations, and five isolated compounds. Concerning the risk of bias, most studies lacked on randomization and blinding. Nociception induced by phlogistic agents was evaluated in most articles, and in five studies it was associated with analysis of inflammatory parameters. In order to investigate the mechanism of action of the natural products used, eight studies evaluated expression of neural or glial molecular markers. Conclusions 16 of 17 natural products found in this review presented positive results, showing their potential for treatment of TMD. However, the lack of methodological clarity can influence these results.
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Produtos Biológicos , Transtornos da Articulação Temporomandibular , Animais , Músculos da Mastigação , Modelos Animais , Articulação TemporomandibularRESUMO
Anxiety disorders appear to involve distinct neurobiological mechanisms and several medications are available against this mental health problem. However, pharmacological therapeutic approaches display undesirable side effects for patients, particularly when long-term therapy is required. Some evidences have suggested that Coriandrum sativum extract (CSE) provide sedative and anxiolytic effects. We investigate if CSE could attenuate anxiety-like behaviors induced by novelty and alarm substance exposures in zebrafish. Adult zebrafish were injected with vehicle, clonazepam, or CSE (25, 50 or 100 mg/kg) and submitted to novel tank test. At the end, saline or alarm substance was added and anxiety-like responses were recorded. Twenty-four hours after, fish were submitted to the light/dark test. Novelty associated with alarm substance exposure decreased distance traveled and total time mobile in novel tank, and CSE (at 50 and 100 mg/kg) prevented these alterations similarly to clonazepam. Alarm substance reduced the time spent in white compartment (p = 0.0193 as compared with vehicle group). Clonazepam and CSE prevented this anxiogenic effect of alarm substance. CSE presents anxiolytic effects against alarm substance-induced locomotor and anxiogenic responses similarly to clonazepam. These data corroborate with the use of this plant in traditional medicine and provides a putative new pharmacological intervention for anxiety disorders.
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Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Coriandrum/química , Medo/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Ansiolíticos/química , Transtornos de Ansiedade/tratamento farmacológico , Comportamento Animal , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
BACKGROUND: Aging is a natural process that, even in the nonattendance of complex diseases, is associated with a numerous behavioral change that attributes reduced muscle mass, power, strength and function. In addition, aging linked to low-grade inflammatory status, characterized by increased plasma concentrations of inflammatory cytokines such as TNF-α and IL-6. Physical exercise is the main non-pharmacological strategy for improving the physical fitness of the aged individuals. However, it is still controversial whether exercise can reduce aging-mediated inflammation. OBJECTIVE: To analyze the effects of functional (FT) and traditional (TT) training practice on muscle power and inflammatory profile in physically active older women. METHODS: The study has been performed for twenty-six weeks in which twenty-four weeks utilized for training sessions and two weeks for physical and biochemical assessments. Forty-three older women (age FT: 64.25 ± 4.70, range: 60-75; TT: 64.90 ± 3.03, range: 60-71; Control: 65.91 ± 5.79, range: 60-75) were randomly divided into three groups: Functional (FT; n = 16); Traditional (TT; n = 16) training groups; and Control Group (CG; n = 11) respectively. Muscle power tests were performed by push (Bench press) and squatting (Squat) actions. The jumping ability was performed through Counter Movement Jump (CMJ). In addition, isometric strength were assessed by Hand Grip Test. Plasma cytokine concentration was measured using flow cytometry. RESULTS: Functional and traditional training sessions subjected to aged women demonstrated a significant enhancement in their physical activity and muscle power. The trained individuals from above two groups showed significant improvements in all analyzed parameters excluding hand-grip. Functional and traditional training exercise reduced the plasma concentrations of TNF-α (FT: p = 0.0001; TT: p = 0.0410) and whereas FT group has reduced IL-6 (p = 0.0072), but did not affect the alterations of pre and post measurements of IL-2 (FT: p = 0.0651; TT: p = 0.2146) and IL-10 values (FT: p = 0.2658; TT: p = 0.3116). There was no significant difference in any of the test parameters between FT and TT groups. CONCLUSION: The functional and traditional training practices showed equivalent beneficial outcomes by increasing muscle power and reducing systemic markers associated with inflammation.
Assuntos
Citocinas , Força da Mão , Força Muscular , Músculo Esquelético/fisiologia , Treinamento Resistido , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , MúsculosRESUMO
Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.
Assuntos
Animais , Feminino , Camundongos , Artrite/induzido quimicamente , Zimosan/administração & dosagem , Dioscorea/efeitos adversos , Diosgenina/efeitos adversos , Osteoartrite/induzido quimicamente , Extratos Vegetais/agonistasRESUMO
We evaluated the effect of the hydroethanolic extract of fruits of Vaccinium macrocarpon (HEVm) in a model of acute pancreatitis (AP) in mice. AP was induced by two injections of L-arginine and animals were treated with HEVm (50, 100, and 200 mg/kg, p.o.) or vehicle (saline) every 24 h, starting 1 h after the induction of AP. Phytochemical analysis of the extract and measurement of inflammatory and oxidative stress parameters, as well as abdominal hyperalgesia, were performed. Catechin, epicatechin, rutin, and anthocyanins were identified in HEVm. Treatment with HEVm decreased L-arginine-induced abdominal hyperalgesia (from 48 to 72 h). Also, treatment with HEVm decreased L-arginine-induced pancreatic edema, pancreatic and pulmonary neutrophil infiltration, and levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6, after 72 h of induction. L-arginine-induced hyperamylasemia and hyperlipasemia were also reduced by the treatment with HEVm in comparison to vehicle-treated group. Moreover, lipoperoxidation, carbonyl radicals, nonprotein sulfhydryl groups, and activity of catalase and superoxide dismutase, but not glutathione peroxidase, were restored by the treatment with HEVm. These results show that treatment with HEVm decreased hyperalgesia and pancreatic/extrapancreatic inflammation and oxidative damage in L-arginine-induced AP, making this extract attractive for future approaches designed to treat this condition.