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INTRODUCTION: The aim of this study was to establish RIs for clinically important markers including superoxide dismutase (SOD), serum copper, zinc, calcium, magnesium, and phosphate in a cohort of healthy Iranian adults. MATERIALS: A subsample from MASHAD cohort study was used to assess serum SOD, copper, zinc, calcium, magnesium and phosphate. Serum SOD was measured according to its inhibitory potential of pyrogallol oxidation. Micro- and macro-minerals were measured using flame atomic absorption spectrometry and a BT3000 autoanalyzer, respectively. Sex- and age-specific RIs were then calculated based on CLSI Ep28-A3 guidelines. RESULTS: Reference value distributions for studied parameters did not demonstrate any age-specific differences that were statistically significant. In addition, sex partitioning was not required for all parameters, apart from serum magnesium, which showed a wider range in females (0.81-1.26 mg/dl) compared with males (0.82-1.23 mg/dl). CONCLUSION: The RIs established in this study can be expected to improve mineral assessment and clinical decision-making in the Iranian adult population.
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Biomarcadores/sangue , Minerais/sangue , Superóxido Dismutase-1/sangue , Adulto , Fatores Etários , Idoso , Cálcio/sangue , Estudos de Coortes , Cobre/sangue , Feminino , Voluntários Saudáveis , Humanos , Irã (Geográfico) , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Monoéster Fosfórico Hidrolases/sangue , Valores de Referência , Fatores Sexuais , Zinco/sangueRESUMO
Background and Aims: Synbiotics found to be beneficial in breast cancer survivors (BCSs) through its antioxidant properties. The aim of this study was to assess the effects of synbiotic supplementation on edema volume and some oxidative markers among obese and overweight patients with BCRL.Method: This randomized double-blind, placebo-controlled trial was conducted on 88 overweight and obese BCSs aged 18-65 years. All the subjects were given a specified low-calorie diet (LCD) and were randomly assigned into two groups to intake 109 CFU/day synbiotic supplement (n = 44) or placebo (n = 44) for 10 wk. Edema volume and serum total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) concentration were measured at baseline and after the 10-wk intervention.Results: Ten-wk supplementation with synbiotics leads to a significant reduction in serum MDA levels (P = 0.001) and an increase in serum SOD concentration (P = 0.007) compared to placebo. No significant changes were observed in serum GPx, TAC, and edema volume between groups.Conclusion: Our findings reveal that 10-wk synbiotic supplementation along with a LCD program-reduced serum MDA levels and elevate the activity of SOD in overweight and obese patients with BCRL. However, its effect on serum GPx, TAC, and edema volume was not significant.
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Antioxidantes/metabolismo , Braço/fisiologia , Neoplasias da Mama/complicações , Sobreviventes de Câncer/estatística & dados numéricos , Linfedema/dietoterapia , Estresse Oxidativo/fisiologia , Simbióticos/administração & dosagem , Adolescente , Adulto , Biomarcadores/sangue , Neoplasias da Mama/patologia , Proteína C-Reativa/metabolismo , Restrição Calórica/normas , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Linfedema/etiologia , Linfedema/patologia , Malondialdeído/sangue , Pessoa de Meia-Idade , Superóxido Dismutase-1/sangue , Adulto JovemRESUMO
Little is known about the contribution of each of the three superoxide dismutase isozymes (SODs) to the total SOD activity in extracellular fluids. This study was aimed to investigate the alterations in concentration/activity of (SODs) in plasma, in context of sex, obesity, exposition to cigarette smoke, and genotypic variability of five selected single nucleotide polymorphisms (SNPs) in genes SOD1, SOD2, SOD3. Men showed higher SOD1 concentration, lower SOD3 concentration and higher total antioxidative capacity (TAC) values. Intersexual variability was observed in concentration of copper, zinc, and cadmium. The obese showed higher total oxidative capacity regardless of sex. An increase in SOD2 activity was coexistent with obesity in men, and exposition to cigarette smoke in non-obese individuals. Additionally, in state of this exposition, Cu,Zn-SOD contribution to the total SOD was lower. Interestingly, over 90% of the obese were of C/T genotype of rs4880 (SOD2). Non-obese of T/T genotype (rs4880) were of lower total SOD activity due to decrease in both Cu,Zn-SOD and Mn-SOD activities. SNP rs2234694 was associated with differences in concentration of SODs, depending on obesity status. Correlations indicate that both TAC and SODs, together, may adapt to insulin resistance and inflammation-derived oxidative stress found in obesity. This topic should be further investigated.
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Obesidade/genética , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase-1/genética , Superóxido Dismutase/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Estresse Oxidativo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/sangue , Superóxido Dismutase-1/metabolismoRESUMO
BACKGROUND This systematic review of the literature and meta-analysis aimed to review the evaluation and monitoring of superoxide dismutase (SOD) activity and its clinical significance in gastric cancer. MATERIAL AND METHODS Systematic review involved searching the PubMed, Embase, Ovid, and the China National Knowledge Infrastructure (CNKI) databases. Search terms included 'superoxide dismutase,' and 'gastric cancer.' Studies that included measurements of SOD activity in peripheral blood samples in patients with SOD activity compared with healthy controls. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS Ten controlled clinical studies were identified that included six studies that measured SOD in serum, three in erythrocytes, and one study that measured SOD on whole blood. Meta-analysis, using the standardized mean difference (SMD) and the 95% confidence interval (CI), showed that patients with gastric cancer had significantly decreased SOD activity when compared with the healthy controls (SMD, -0.840; 95% CI, -1.463 to -0.218; p=0.008). Subgroup analysis was conducted on SOD distribution in the blood (erythrocyte: SMD, -1.773; 95% CI, -2.504 to -1.042; p=0.000) (serum SMD, -0.322; 95% CI, -1.006-0.361; p=0.355) (whole blood: SMD, -1.251; 95% CI, -1.731 to -0.771; p=0.000) and for male subjects (SMD, -2.090; 95% CI, -2.725 to -1.456; p<0.001). CONCLUSIONS Meta-analysis showed that SOD measurements from blood samples, especially in erythrocytes, had potential as a diagnostic and monitoring parameter in patients with gastric cancer.
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Neoplasias Gástricas/enzimologia , Superóxido Dismutase/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Neoplasias Gástricas/sangue , Superóxido Dismutase/sangue , Superóxido Dismutase-1/sangue , Superóxido Dismutase-1/metabolismoRESUMO
To investigate the role of S100B, oxidative stress and the apoptosis signaling pathways in the sevoflurane induced neuroprotective effect on stroke. The brain injury, molecular and cellular damage, and functional recovery were investigated upon ischemic brain injury followed by sevoflurane treatment. Longa rodent stroke scales was used to quantify neurological deficits. TTC staining was used to measure infarct volume of brain tissue. Absolute brain water content was measured by wet/dry weight method. The neuronal morphological change was assessed by H and E staining. The spatial learning and memory ability were measured by water maze test. Serum proteins including S100B, GSH-PX, SOD, Bcl-2, Bax, Caspase-3 were measured by ELISA. The level of NOS and NO in serum was determined by colorimetric method. Compared with control, the serum proteins including S100B, Bax, NO, Caspase-3, and NOS activity in cerebral infarction rats increased significantly while SOD, GSH-PX, and Bcl-2 decreased significantly. Diabetic mellitus complicated with cerebral infarction rats showed more dramatic increase for S100B, Bax, NO, Caspase-3, and NOS activity and dramatic decrease for SOD, GSH-PX, and Bcl-2. Interestingly, sevoflurane reduced the changes significantly. The S100B level positively correlated with brain damage, NO, Bax, caspase-3, and NOS activity but negatively correlated with SOD, Bax, and GSH-PX. Brain damage in sevoflurane groups decreased while behavior outcomes including Longa neurologic score, learning, and memory increased significantly. The neuroprotective effect of sevoflurane is associated with defense mechanisms against free radical-induced oxidative stress and inhibition of apoptosis. S100B protein correlated with oxidative stress and the apoptosis signaling pathways.
Assuntos
Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Sevoflurano/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/sangue , Lesões Encefálicas/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Caspase 3/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Dieta , Modelos Animais de Doenças , Humanos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Ratos , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Superóxido Dismutase-1/sangue , Proteína X Associada a bcl-2/sangueRESUMO
Oxidative status is attributed to endothelial dysfunction and might be one of the key mechanisms of endothelial dysfunction in acromegaly. In this study, we aimed to investigate the effect of acromegaly on superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels, and the possible influence of human manganese superoxide dismutase (MnSOD) polymorphism on these levels. 51 acromegaly patients and 57 age and sex matched healthy subjects were recruited to the study in Bezmialem Vakif University Hospital between 2011 and 2014. The median SOD and TAC levels were 42.7 (33-60) pg/mL and 1,313.7 (155-1,902) µM in acromegaly; and 46.3 (38-95) pg/mL and 1,607.3 (195-1,981) µM in healthy subjects (p < 0.001, p < 0.001). SOD levels were decreased in controlled and uncontrolled patients compared to healthy subjects (p = 0.05 and p = 0.002, respectively). Controlled and uncontrolled acromegaly displayed significantly decreased levels of TAC compared to healthy subjects (p < 0.05 and p < 0.001, respectively). SOD levels were not associated with MnSOD polymorphisms in acromegaly. In conclusion, this study showed that acromegaly was associated with decreased levels of SOD and TAC, and controlling the disease activity could not adequately improve these levels.
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Acromegalia/sangue , Adenoma/fisiopatologia , Antioxidantes/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/fisiopatologia , Estresse Oxidativo , Superóxido Dismutase-1/sangue , Superóxido Dismutase/genética , Acromegalia/etiologia , Acromegalia/metabolismo , Acromegalia/prevenção & controle , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Estudos de Associação Genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Hipófise/diagnóstico por imagem , Hipófise/patologia , Polimorfismo de Nucleotídeo Único , Indução de Remissão , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/metabolismo , Carga Tumoral , TurquiaRESUMO
Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies.
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Analgésicos Opioides/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Buprenorfina/farmacologia , Estresse Oxidativo , Adulto , Idoso , Animais , Antioxidantes/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Catalase/sangue , Estudos de Coortes , Colágeno/química , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Inflamação , Masculino , Metaloproteinase 3 da Matriz/sangue , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/sangue , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase-1/sangueRESUMO
INTRODUCTION: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. MATERIALS AND METHODS: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn- superoxide dismutase (Cu,Zn-SOD) in serum. RESULTS: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu,Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. CONCLUSION: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.
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Asma/etiologia , Estresse Oxidativo , Poluição por Fumaça de Tabaco/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Asma/metabolismo , Biomarcadores/análise , Criança , Pré-Escolar , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Eczema/etiologia , Feminino , Humanos , Masculino , Peroxidase/sangue , Superóxido Dismutase-1/sangue , Adulto JovemRESUMO
Role in the pathogenesis of atherosclerosis play a reactive oxygen species. In the case of disturbance of dynamic balance between their production and antioxidant defense mechanisms comes to undesirable consequences - oxidative stress. Excessive exercise can, among others, disrupting the balance. AIM: The aim of the study was to evaluate the exponents of the processes of oxidation - reduction of blood in patients with ACS undergoing rehabilitation in a hospital setting. MATERIALS AND METHODS: The study included 25 patients after ACS STEMI, including 19 men and 6 women, aged 51.5±6.5 years, underwent rehabilitation in the Department of Internal Medicine and Cardiac Rehabilitation, University Hospital im. WAM in Lodz. Blood samples were taken after an initial exercise test (I) and after the final exercise test (IV). Marked: SOD-1, CAT, GPX- in red blood cells, plasma antioxidant activity (TAS) and the concentration of MDA in the red blood cells. Cardiac rehabilitation program included 15 interval training, each lasting 40-45 minutes. RESULTS: The results were statistically analyzed. For the statistically significant level of p<0.05. No significant effect of cardiac rehabilitation on the activity of GPX, SOD-1, MDA and antioxidant activity of plasma. There was only a significant impact on the rehabilitation of CAT activity (p=0.002). CONCLUSIONS: Properly conducted cardiac rehabilitation does not disturb the balance of oxidation - reduction of blood in patients with ACS. Exercise should be selected in such a way that this balance is maintained.
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Síndrome Coronariana Aguda/reabilitação , Terapia por Exercício , Estresse Oxidativo , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/metabolismo , Antioxidantes/análise , Biomarcadores/sangue , Reabilitação Cardíaca , Catalase/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase-1/sangueRESUMO
BACKGROUND: Oxidative stress is thought to be involved in the pathogenesis of microalbuminuria in Sickle cell anemia (SCA). Antioxidant enzymes such as glutathione peroxidase (GPx) and Cu-Zn superoxide dismutase (SOD) may play an important protective role. This study aimed to evaluate the association between albuminuria and these two antioxidant enzymes. METHODS: We consecutively recruited Steady state children aged between 2 and 18 years old with established diagnosis of homozygous SCA in two hospitals of Kinshasa/DR Congo. The relationship between Urinary Albumin Creatinine Ratio (UACR) and other variables of interest (age, systolic blood pressure, diastolic blood pressure, plasma GPx and Cu-Zn SOD, free plasmatic hemoglobin, LDH, indirect bilirubin, white blood cells (WBC), percentage of fetal hemoglobin, serum iron, ferritin, CRP) was analyzed by Bivariate correlation (Pearson's correlation coefficient). Microalbuminuria was defined by urine albumin/creatinine ratio between 30 and 299 mg/g. RESULTS: Seventy Steady state Black African children with SCA (56% boys; average age 9.9 ± 4.3 years; 53% receiving hydroxyurea) were selected. Prevalence of microalbuminuria was 11.8%. LDH (r = 0.260; p = 0.033) and WBC count (r = 0.264; p = 0.033) were positively correlated with UACR whereas GPx (- 0.328; p = 0.007) and Cu-Zn SOD (- 0.210; p = 0.091) were negatively correlated with UACR. CONCLUSIONS: Albuminuria is associated with decreased antioxidant capacity and increased levels of markers of hemolysis and inflammation. Therefore, strategies targeting the reduction of sickling and subsequent hemolysis, oxidative stress and inflammation could help preventing or at least delaying the progression of kidney disease in SCA children.
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Albuminúria/urina , Anemia Falciforme/metabolismo , Glutationa Peroxidase/sangue , Superóxido Dismutase-1/sangue , Adolescente , Albuminúria/enzimologia , Anemia Falciforme/genética , Biomarcadores/sangue , Criança , Pré-Escolar , Creatinina/urina , Estudos Transversais , Feminino , Hemólise , Homozigoto , Humanos , Inflamação/sangue , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Masculino , Estresse OxidativoRESUMO
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.
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Angiotensina II/metabolismo , Antioxidantes/uso terapêutico , Fenofibrato/uso terapêutico , Resistência à Insulina/fisiologia , Síndrome Metabólica/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Catalase/sangue , Modelos Animais de Doenças , Insulina/sangue , Masculino , NADPH Oxidase 4 , NADPH Oxidases/sangue , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Superóxido Dismutase-1/sangue , Triglicerídeos/sangueRESUMO
Aims: To evaluate the correlation of nesfatin-1, GSH and SOD levels with ß-cell insulin secretion and their influence on insulin secretion in the development of type 2 diabetes mellitus (T2DM). Materials and methods: 75 patients with T2DM, 67 with prediabetes and 37 heathy participants were recruited in this study. Serum levels of nesfatin-1, GSH and SOD were quantified and statistically analyzed. Results: The levels of nesfatin-1, GSH and SOD in T2DM were significantly decreased (P < 0.001) compared to either in prediabetes or in healthy control, and significant reduction of these biomarkers was also observed in prediabetes when compared to the control (P < 0.001). Circulating nesfatin-1, GSH and SOD were not only strongly correlated with ß-cell insulin secretion, but also exerted remarkable influence on the secretion. Conclusion: Serum nesfatin-1, GSH and SOD are important factors involving insulin secretion in the development of T2DM, which may help provide new ideas for forthcoming investigations on the roles of these factors in pathogenesis of T2DM, as well as for active prediction and prevention of prediabetes before it develops into overt T2DM.
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Diabetes Mellitus Tipo 2 , Glutationa/metabolismo , Nucleobindinas/metabolismo , Estado Pré-Diabético , Superóxido Dismutase-1/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Glutationa/sangue , Humanos , Secreção de Insulina , Nucleobindinas/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/metabolismo , Superóxido Dismutase , Superóxido Dismutase-1/sangueRESUMO
BACKGROUND AND AIMS: Endothelial cell injury causes vascular barrier dysfunction and leukocyte recruitment to the underlying tissue. Bone morphogenetic protein 4 (BMP-4) is a transforming growth factor that exerts pro-inflammatory effects on the endothelium. Here, we investigated the effects of BMP-4 on endothelial cell (EC) migration following balloon injury in SD rats. METHODS: An intimal hyperplasia model was established using balloon injury. Hematoxylin-eosin staining (HE) and silver staining were used to detect the alteration of endothelial cells recovery after balloon injury. Serum BMP-4 levels were assessed by ELISA. Human umbilical vein endothelial cells (HUVECs) were cultured. MTT assay was used to measure cell viability. Protein expression was detected by Western blot. Intracellular reactive oxygen species (ROS) was detected by dichloro-dihydro-fluorescein diacetate (DCFH-DA). HUVECs migration was measured via transwell assay and scratch wound assay. RESULTS: The results indicated that BMP-4 inhibition significantly decreased total plasma activity of BMP-4 and reduced neointimal hyperplasia by stimulating endothelial cell migration, but did not affect the medial area following balloon injury. BMP-4 suppressed the formation of ROS via forkhead box O3 (FoXO-3)/superoxide dismutase 1 (SOD-1). In vitro, a high level of ROS induced by BMP-4 impeded HUVECs migration. CONCLUSIONS: The results suggest that BMP-4 inhibition is a potential means of preventing intimal hyperplasia formation after balloon injury.
Assuntos
Proteína Morfogenética Óssea 4 , Células Endoteliais da Veia Umbilical Humana , Animais , Proteína Morfogenética Óssea 4/antagonistas & inibidores , Proteína Morfogenética Óssea 4/biossíntese , Proteína Morfogenética Óssea 4/sangue , Lesões das Artérias Carótidas/sangue , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Movimento Celular , Células Cultivadas , Proteína Forkhead Box O3/biossíntese , Proteína Forkhead Box O3/sangue , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hiperplasia , Neointima/sangue , Neointima/metabolismo , Neointima/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase-1/biossíntese , Superóxido Dismutase-1/sangueRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Biomarcadores/sangue , Fatores de Crescimento de Fibroblastos/sangue , Regulação da Expressão Gênica , Músculo Esquelético/metabolismo , Superóxido Dismutase-1/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/metabolismo , Animais , Biomarcadores/metabolismo , Biópsia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Superóxido Dismutase-1/metabolismo , Regulação para Cima , Adulto JovemRESUMO
OBJECTIVE: The rs2234694 and 50 bp insertion/deletion (Ins/Del) polymorphisms of the SOD1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of SOD1 gene polymorphisms (rs2234694 and 50 bp Ins/Del) in BC patients in the Mexican population. MATERIALS AND METHODS: The SOD1 polymorphisms were determined by Polymerase Chain Reaction (PCR) in Mexican healthy subjects and BC patients. RESULTS: The rs2234694 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the AC genotype (p<0.0001), the AC/CC genotype (dominant model: p<0.0001), and the C allele (p<0.0001). The 50 bp Ins/Del polymorphism was associated with BC susceptibility for the Del allele (p=0.048), although the association between the dominant model AC/CC (rs2234694) and BC patients was evident for menopause [adjusted odds ratio (OR) 1.65 (95% CI 1.05-2.7); p=0.048], Ki-67 (≥15%) (OR1.9, 95% CI 1.14- 3.16, p=0.016), and the presence of DM2 (OR 2.4, 95% CI 1.35- 4.31, p=0.003). A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for estrogen receptor (ER) and progesterone receptor (PR), carrying the AC genotypes (OR 0.47, 95% CI 0.23-0.94, p= 0.033) and CC (OR 0.11, 95% CI 0.013-1.07, p=0.047). The association between the InsDel/DelDel (dominant model; 50 bp Ins/Del) genotype and BC with metastatic lymph nodes (OR 1.5, 95% CI 1.1-2.25, p=0.019), hematologic toxicity (OR 1.5, 95%CI 1.1-2.23, p=0.015), gastric toxicity (OR 1.5, 95%CI 1.1-2.07, p=0.030), and Ki-67 (≥15%) (OR1.6, 95%CI 1.2-2.26, p=0.002) was evident, indicating that these factors may contribute significantly to BC risk. The C/Ins haplotype was also associated with BC susceptibility (OR3.47, 95% CI 1.62-7.74, p=0.001). CONCLUSIONS: rs2234694 and 50 bp Ins/Del polymorphisms in the SOD1 gene were associated with BC susceptibility in a Mexican population. A protective association for BC of the rs2234694 polymorphism was observed in patients younger than 50 years positive for ER and PR, carrying the AC genotypes. The haplogenotypes AA/InsIns and AC/InsDel could contribute significantly to BC risk in gastric and hematologic toxicities, metastatic lymph nodes, and the presence of DM2 in the Mexican population analyzed.
Assuntos
Neoplasias da Mama/genética , Polimorfismo Genético/genética , Superóxido Dismutase-1/genética , Alelos , Neoplasias da Mama/patologia , Feminino , Humanos , México , Pessoa de Meia-Idade , Fatores de Risco , Superóxido Dismutase-1/sangueRESUMO
The aim of the present study was to assess the oxidative stress level and chromosomal damage induced by occupational exposure to low dose ionizing radiation (LDIR). Two hundred and eighteen hospital workers occupationally exposed to LDIR were included in this study, along with 118 healthy age- and gender-comparable controls. Occupational dosimetry records were collected over the last year and revealed that the accumulated annual dose for each hospital worker was below the permissible limit of the International Commission on Radiological Protection (ICRP). The individuals' oxidative and antioxidative status were determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. The effect of radiation on chromosomal integrity was measured by the frequency of micronuclei (MN) formation using the cytokinesis block technique. Our results showed that the activities of CuZn-SOD and CAT enzymes and MDA levels observed in the hospital workers were higher than those in the controls (p < 0.05). We did not find significant difference in GSH-Px enzyme activity between the two groups (p = 0.247). A higher frequency of MN was found in exposed groups than in the controls [3(1-5) versus 2(0.75-4) ; p<0.001]. The difference was significant for males (p = 0.012), but not females (p = 0.14). Multiple linear regression analysis showed differences in the oxidant activities and MN frequency between hospital workers and controls adjusted for age, gender, smoking status and drinking status. Correlation analysis indicated that the frequency of MN was positively associated with MDA levels (p < 0.05). Altogether, these results support the detrimental effects of chronic low dose radiation in humans, which involves the induction of oxidative stress and chromosomal damage.
Assuntos
Antioxidantes/metabolismo , Aberrações Cromossômicas/efeitos da radiação , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos da radiação , Adulto , Antioxidantes/efeitos da radiação , Catalase/sangue , Feminino , Glutationa Peroxidase/sangue , Hospitais , Humanos , Masculino , Malondialdeído/sangue , Prontuários Médicos , Pessoa de Meia-Idade , Doses de Radiação , Radiação Ionizante , Radiometria , Superóxido Dismutase-1/sangueRESUMO
To remedy carotid artery stenosis and prevent stroke surgical intervention is commonly used, and the gold standard being carotid endarterectomy (CEA). During CEA cerebrovascular hemoglobin oxygen saturation decreases and when this decrease reaches critical levels it leads to cerebral hypoxia that causes neuronal damage. One of the proposed mechanism that affects changes during CEA and contribute to acute brain ischemia (ABI) is oxidative stress. The increased production of reactive oxygen species and reactive nitrogen species during ABI may cause an unregulated inflammatory response and further lead to structural and functional injury of neurons. Antioxidant activity are involved in the protection against neuronal damage after cerebral ischemia. We hypothesized that neuronal injury and poor outcomes in patients undergoing CEA may be results of oxidative stress that disturbed function of antioxidant enzymes and contributed to the DNA damage in lymphocytes.
Assuntos
Isquemia Encefálica/enzimologia , Catalase/biossíntese , Endarterectomia das Carótidas/efeitos adversos , Hipóxia Encefálica/enzimologia , Complicações Intraoperatórias/enzimologia , Linfócitos/enzimologia , Superóxido Dismutase-1/biossíntese , Superóxido Dismutase/biossíntese , Isquemia Encefálica/etiologia , Estenose das Carótidas/enzimologia , Estenose das Carótidas/cirurgia , Catalase/sangue , Catalase/genética , Dano ao DNA , Radicais Livres , Regulação Enzimológica da Expressão Gênica , Humanos , Hipóxia Encefálica/etiologia , Complicações Intraoperatórias/etiologia , Mitocôndrias/metabolismo , Modelos Biológicos , Estresse Oxidativo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/etiologia , Superóxido Dismutase/sangue , Superóxido Dismutase/genética , Superóxido Dismutase-1/sangue , Superóxido Dismutase-1/genéticaRESUMO
The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4 mg/kg deoxynivalenol of basal diet (DON), (3) 5 g/kg baicalin-copper of basal diet (BCU); and (4) 4 mg/kg deoxynivalenol + 5 g/kg baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-κB in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.
Assuntos
Antioxidantes/metabolismo , Flavonoides/farmacologia , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade , Aminoácidos/sangue , Ração Animal , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Cobre/química , Dieta , Suplementos Nutricionais , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Íleo/metabolismo , Jejuno/citologia , Jejuno/enzimologia , Jejuno/metabolismo , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Soro/enzimologia , Soro/metabolismo , Superóxido Dismutase-1/sangue , Suínos , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismoRESUMO
BACKGROUND AND AIM: Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25âg of phenols-rich EVOO (p-EVOO). METHODS: The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25âg of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2âh after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS: A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (Pâ<â0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (Pâ<â0.05). CONCLUSION: The current study shows that intake of 25âg of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.Trial registration ClinicalTrials.gov NCT01890070.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipoproteínas LDL/sangue , Nutrigenômica/métodos , Azeite de Oliva/metabolismo , Estresse Oxidativo/genética , Fenóis/sangue , Álcool Feniletílico/análogos & derivados , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Catalase/sangue , Catalase/genética , Dieta Saudável , Dieta Mediterrânea , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Azeite de Oliva/administração & dosagem , Álcool Feniletílico/sangue , Período Pós-Prandial , Fatores de Proteção , Fatores de Risco , Cidade de Roma , Superóxido Dismutase-1/sangue , Superóxido Dismutase-1/genética , Fatores Estimuladores Upstream/sangue , Fatores Estimuladores Upstream/genética , Adulto JovemRESUMO
Chia is a good source of calcium, however it is not been previously reported its bioavailability associated with an inflammatory condition. Thus, the present study evaluated the effect of chia on calcium bioavailability, inflammation, and oxidative stress in Wistar rats fed a high-fat diet or standard diet for 35â¯days. Chia consumption resulted in lower calcium balance and calcium absorption and retention rates. In addition, the urinary calcium concentration was lower in groups that were fed chia. The bone resistance of animals feed chia was lower than that in rats fed the standard diet receiving calcium carbonate. Animals that were fed chia showed lower total, very low-density lipoprotein, and low-density lipoprotein cholesterol levels than animalsfed calcium carbonate. Animals fed standard diet showed higher superoxide dismutase plasma concentrations than animals in the high fat calcium carbonate group. PPAR-α protein levels were higher in animals fed chia whereas TNF-α and IL-10 were lower in these animals. NFκB mRNA expression and protein levels were lower in the groups that received chia compared with HFDâ¯+â¯CC. Chia intake presented low calcium bioavailability regardless of the type of diet consumed and was able to improved inflammation and the lipid profile in young Wistar rat. Besides this, the consumption of this seed increased the activity of antioxidants enzymes.