RESUMO
Ferroptosis is a novel type of iron-dependent programmed cell death characterised by intracellular iron overload, increased lipid peroxidation and abnormal accumulation of reactive oxygen species.It has been implicated in the progression of several diseases including cancer, ischaemia-reperfusion injury, neurodegenerative diseases and liver disease. The etiology of endometriosis (EMS) is still unclear and is associated with multiple factors, often accompanied by various forms of cell death and a complex microenvironment. In recent decades, the role of non-traditional forms of cell death, represented by ferroptosis, in endometriosis has come to the attention of researchers. This article reviews the transitional role of iron homeostasis in the development of ferroptosis, the characteristics and regulatory mechanisms of ferroptosis, and focuses on summarising the links between iron death and various pathogenic mechanisms of EMS, including oxidative stress, dysregulation of lipid metabolism, inflammation, autophagy and epithelial-mesenchymal transition. The possible applications of ferroptosis in the treatment of EMS, future research directions and current issues are discussed with the aim of providing new ideas for further understanding of EMS.
Assuntos
Endometriose , Ferroptose , Ferro , Estresse Oxidativo , Ferroptose/fisiologia , Endometriose/patologia , Endometriose/metabolismo , Humanos , Feminino , Ferro/metabolismo , Estresse Oxidativo/fisiologia , Peroxidação de Lipídeos/fisiologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Autofagia/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Metabolismo dos Lipídeos/fisiologiaRESUMO
BACKGROUND Either a reduction in antioxidant levels or an accumulation of reactive oxygen species can heighten susceptibility to oxidative damage in disc cells. To date, no research has investigated the levels of lipid peroxidation products (thiobarbituric acid reactive substances [TBARs]), reduced glutathione (GSH), and glutathione peroxidase (GPx) in excised human lumbar disc tissues affected by degenerative disease. Therefore, this study aimed to evaluate lipid peroxidation products in excised disc tissues from patients with degenerative disc disease. MATERIAL AND METHODS Forty-two patients were enrolled. Patients were divided into lumbar disc degeneration (LDD) and nonlumbar disc degeneration (nonLDD) groups according to Pfirrmann classification. Intervertebral discs were obtained from all patients during the operation and were homogenized for analysis. TBARs levels were measured using fluorometry. GSH levels and GPx activity were quantified spectrophotometrically using a kinetic method. RESULTS TBARs levels in excised discs from LDD patients (5.18±4.14) were significantly higher than those from nonLDD patients (2.56±1.23, P=0.008). The levels of TBARs tended to increase with the severity of degeneration according to the Pfirrmann classification. However, these 2 groups showed no significant differences in reduced glutathione levels or glutathione peroxidase activity (P>0.05). Patients with LDD exhibited a worse health-related quality of life, reflected in lower utility and EQ-VAS scores and higher Oswestry disability index scores. CONCLUSIONS There was a notable increase in lipid peroxidation products in the excised intervertebral discs of patients with LDD. This finding suggests that oxidative stress may contribute to the development of disc degeneration.
Assuntos
Glutationa Peroxidase , Glutationa , Degeneração do Disco Intervertebral , Disco Intervertebral , Peroxidação de Lipídeos , Vértebras Lombares , Estresse Oxidativo , Substâncias Reativas com Ácido Tiobarbitúrico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Peroxidação de Lipídeos/fisiologia , Vértebras Lombares/metabolismo , Estresse Oxidativo/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , IdosoRESUMO
The interaction of iron and oxygen is an integral part of the development of life on Earth. Nonetheless, this unique chemistry continues to fascinate and puzzle, leading to new biological ventures. In 2012, a Columbia University group recognized this interaction as a central event leading to a new type of regulated cell death named "ferroptosis." The major feature of ferroptosis is the accumulation of lipid hydroperoxides due to (1) dysfunctional antioxidant defense and/or (2) overwhelming oxidative stress, which most frequently coincides with increased content of free labile iron in the cell. This is normally prevented by the canonical anti-ferroptotic axis comprising the cystine transporter xCT, glutathione (GSH), and GSH peroxidase 4 (GPx4). Since ferroptosis is not a programmed type of cell death, it does not involve signaling pathways characteristic of apoptosis. The most common way to prove this type of cell death is by using lipophilic antioxidants (vitamin E, ferrostatin-1, etc.) to prevent it. These molecules can approach and detoxify oxidative damage in the plasma membrane. Another important aspect in revealing the ferroptotic phenotype is detecting the preceding accumulation of lipid hydroperoxides, for which the specific dye BODIPY C11 is used. The present manuscript will show how ferroptosis can be induced in wild-type medulloblastoma cells by using different inducers: erastin, RSL3, and iron-donor. Similarly, the xCT-KO cells that grow in the presence of NAC, and which undergo ferroptosis once NAC is removed, will be used. The characteristic "bubbling" phenotype is visible under the light microscope within 12-16 h from the moment of ferroptosis triggering. Furthermore, BODIPY C11 staining followed by FACS analysis to show the accumulation of lipid hydroperoxides and consequent cell death using the PI staining method will be used. To prove the ferroptotic nature of cell death, ferrostatin-1 will be used as a specific ferroptosis-preventing agent.
Assuntos
Compostos de Boro , Neoplasias Cerebelares , Cicloexilaminas , Meduloblastoma , Fenilenodiaminas , Humanos , Peroxidação de Lipídeos/fisiologia , Antioxidantes/farmacologia , Ferro/metabolismo , Glutationa/metabolismo , Peróxidos Lipídicos , FenótipoRESUMO
INTRODUCTION: The objective of the study was to explore the molecular mechanism of long noncoding RNA (lncRNA) LINC00472 in Alzheimer's disease (AD) and identify potential novel targets for AD therapy. METHOD: Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experiments. The content of Aß protein and tau protein hyperphosphorylation were examined in hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aß25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and tau protein in AD model cells were examined by ROS assay, MDA assay, Western blot, and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS: The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aß and tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was upregulated, GPX4 protein and mRNA were decreased, and phosphorylation of tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the upregulation of lipid peroxide, decreased the level of GPX4, and enhanced tau protein phosphorylation, and reduced iron accumulation in AD cells. CONCLUSIONS: LINC00472 affects ferroptosis in AD by regulating iron accumulation in neuronal cells.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Modelos Animais de Doenças , Ferroptose , Proteína Forkhead Box O1 , Neurônios , RNA Longo não Codificante , Proteínas tau , Ferroptose/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Camundongos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Neurônios/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Proteínas tau/genética , Humanos , Hipocampo/metabolismo , Masculino , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/fisiologia , Camundongos Endogâmicos C57BLRESUMO
Although the role of ferroptosis in killing tumor cells is well established, recent studies indicate that ferroptosis inducers also sabotage anti-tumor immunity by killing neutrophils and thus unexpectedly stimulate tumor growth, raising a serious issue about whether ferroptosis effectively suppresses tumor development in vivo. Through genome-wide CRISPR-Cas9 screenings, we discover a pleckstrin homology-like domain family A member 2 (PHLDA2)-mediated ferroptosis pathway that is neither ACSL4-dependent nor requires common ferroptosis inducers. PHLDA2-mediated ferroptosis acts through the peroxidation of phosphatidic acid (PA) upon high levels of reactive oxygen species (ROS). ROS-induced ferroptosis is critical for tumor growth in the absence of common ferroptosis inducers; strikingly, loss of PHLDA2 abrogates ROS-induced ferroptosis and promotes tumor growth but has no obvious effect in normal tissues in both immunodeficient and immunocompetent mouse tumor models. These data demonstrate that PHLDA2-mediated PA peroxidation triggers a distinct ferroptosis response critical for tumor suppression and reveal that PHLDA2-mediated ferroptosis occurs naturally in vivo without any treatment from ferroptosis inducers.
Assuntos
Neoplasias , Animais , Camundongos , Modelos Animais de Doenças , Peroxidação de Lipídeos/fisiologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Abstract Background: Obesity can be characterized by low-grade chronic inflammation and is associated with an excesso production of reactive oxygen species, factors that contribute to coronary heart disease and other cardiomyopathies. Objective: To verify the effects of resistance exercise training on oxidative stress and inflammatory parameters on mice with obesity induced by a high-fat diet (HFD). Methods: 24 Swiss mice were divided into 4 groups: standard diet (SD), SD + resistance exercise (SD + RE), diet-induced obesity (DIO), DIO + RE. The animals were fed SD or HFD for 26 weeks and performed resistance exercises in the last 8 weeks of the study. The insulin tolerance test (ITT) and body weight monitoring were performed to assess the clinical parameters. Oxidative stress and inflammation parameters were evaluated in the cardiac tissue. Data were expressed by mean and standard deviation (p < 0.05). Results: The DIO group had a significant increase in reactive oxygen species levels and lipid peroxidation with reduction after exercise. Superoxide dismutase and the glutathione system showed no significant changes in DIO animals, with an increase in SD + RE. Only catalase activity decreased with both diet and exercise influence. There was an increase in tumor necrosis factor-alpha (TNF-α) in the DIO group, characterizing a possible inflammatory condition, with a decrease when exposed to resistance training (DIO+RE). Conclusion: The DIO resulted in a redox imbalance in cardiac tissue, but the RE was able to modulate these parameters, as well as to control the increase in TNF-α levels.
Resumo Fundamento: A obesidade pode ser caracterizada por uma inflamação crônica de baixo grau e está associada à produção excessiva de espécies reativas de oxigênio, fatores que contribuem para doenças coronarianas e outras cardiomiopatias. Objetivo: Verificar os efeitos do treinamento resistido sobre os parâmetros de estresse oxidativo e parâmetro inflamatório em camundongos com obesidade induzida por dieta hiperlipídica (DIO). Métodos: 24 camundongos Swiss foram divididos em 4 grupos: dieta padrão (DP), DP + exercício resistido (DP+ER), obesidade induzida por DIO, DIO + ER. Os animais foram alimentados por 26 semanas com DP ou hiperlipídica realizando treinamento resistido nas 8 semanas finais do estudo. Para avaliar parâmetros clínicos foi realizado o teste de tolerância à insulina (TTI) e monitoramento do peso corporal. No tecido cardíaco foram avaliados parâmetros de estresse oxidativo e inflamação. Dados expressos por média e desvio padrão (p < 0,05). Resultados: O grupo DIO teve um aumento significativo nos níveis espécies reativas e peroxidação lipídica com redução após o exercício. A superóxido dismutase e o sistema glutationa não demonstraram alterações importantes nos animais DIO, com elevação perante DP+ER. Somente a atividade da catalase reduziu tanto com influência da dieta como do exercício. Ocorreu um aumento do fator de necrose tumoral-alfa (TNF-α) no grupo DIO, caracterizando um possível quadro inflamatório, com redução quando expostos ao treino resistido (DIO+ER). Conclusão: A DIO ocasionou um desequilíbrio redox no tecido cardíaco, porém o ER foi capaz de modular estes parâmetros, bem como controlar o aumento do TNF-α.
Assuntos
Animais , Masculino , Ratos , Peroxidação de Lipídeos/fisiologia , Fator de Necrose Tumoral alfa/análise , Estresse Oxidativo/fisiologia , Treinamento Resistido , Dieta Hiperlipídica/efeitos adversos , Miocárdio/química , Condicionamento Físico Animal , Fatores de Tempo , Resistência à Insulina , Inflamação/fisiopatologiaRESUMO
Abstract Purpose: To evaluate the effects of oxidative stress in pregnant rats submitted to acute and chronic stress, relating to alterations in the uterus, placenta and fetus. Methods: Twenty-four female Wistar albino (Rattus norvegicus), were divided into four groups, for induction of oxidative stress the animals were submitted to cold and physical immobilization. Plasma fasting glucose and MDA were determined in all groups and the fetuses and placentas were measured. Results: There were no statistical differences in the levels of malonic dialdehyde (MDA), however the averages of chronic stress group were higher compared to control groups, which could explain the observed adverse effects; there was no correlation between puppies' size, the weight of the placenta and MDA values. Conclusions: Chronic stress causes adverse effects, when compared to control groups; chronic stress group had fetuses, placentas and number of puppies, significantly lower compared to other groups. The rats exposed to chronic stress, also presented a higher frequency of fetal resorption.
Assuntos
Animais , Masculino , Feminino , Gravidez , Ratos , Placenta/fisiopatologia , Estresse Fisiológico/fisiologia , Útero/fisiopatologia , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Feto/fisiopatologia , Glicemia/análise , Doença Aguda , Doença Crônica , Ratos Wistar , Peso Fetal/fisiologia , Modelos Animais de DoençasRESUMO
Abstract Purpose: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. Methods: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. The blood was collected, for biochemical analysis of AST, and the liver removed for assessment of TBARS and nitrite, and of histology. Results: After the I/R, the animal fed with MCD diet presented higher AST levels (MCD-I/R: 967±349U/L / ob/ob-I/R: 606±18 U/L / I/R: 311±172 U/L), TBARS (MCD-I/R: 7±1 nM/mg protein / ob/ob-I/R: 3±1 nM/mg protein / I/R: 3±1 nM/mg protein) and nitrite (MCD-I/R: 614±87 µg/mL / ob/ob-I/R: 512±81 µg/mL / I/R: 459±29 µg/mL) than the ob/ob mice, when both groups were compared to animals fed with standard diet. Regarding histology, the steatosis level (azonal macrovesicular steatosis of level 3 - >66%) and hepatic fibrosis (periportal and perisinusoidal of level 2) was also more intense, but both animal models presented lobular inflammation of level 3 (>66%). Conclusions: The murine model fed with MCD diet is suitable for the assessment of oxidative stress in hepatic I/R injury associated with the nonalcoholic fatty liver disease. Although both murine models showed inflammatory infiltrate and macro and micro vesicular steatosis.
Assuntos
Animais , Masculino , Ratos , Peroxidação de Lipídeos/fisiologia , Traumatismo por Reperfusão/metabolismo , Estresse Oxidativo/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Nitritos/metabolismo , Traumatismo por Reperfusão/patologia , Modelos Animais de Doenças , Hepatopatia Gordurosa não Alcoólica/patologia , Camundongos Endogâmicos C57BLRESUMO
Abstract: Background: Previous studies have shown oxidative stress in pemphigus vulgaris and pemphigus foliaceus, nevertheless, it remains unknown whether a similar response is characteristic of endemic pemphigus foliaceus in Peru. Objectives: To determine the oxidative stress response in endemic pemphigus foliaceus patients and subjects with positive for anti-desmoglein1 antibodies (anti-dsg1) from endemic areas of Peru. Subjects and Methods: This is a cross-sectional study. The study population included 21 patients with Endemic Pemphigus foliaceus and 12 healthy subjects with anti-dsg1 antibodies from the Peruvian Amazon (Ucayali), as well as 30 healthy control subjects. Malondialdehyde, an indicator of lipid peroxidation by free radicals, was measured in serum. Results: We collected 21 cases of endemic pemphigus foliaceus, 15 of them with active chronic disease and 6 in clinical remission. Serum malondialdehyde values in patients with chronic active evolution and healthy subjects with anti-dsg1 antibodies were statistically higher than those of healthy controls (p<0.001). There was no significant difference between serum values of localized and generalized clinical forms. Study limitations: The main limitation of this present study is the small number of patients with endemic pemphigus and healthy subjects positive for desmoglein 1 antibodies. Conclusions: The increased serum levels of malondialdehyde in patients with chronic active endemic pemphigus foliaceus and healthy subjects from endemic areas with anti-dsg1 antibodies may suggest a contribution of systemic lipid peroxidation in the pathogenesis of endemic pemphigus foliaceus.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Pênfigo/imunologia , Pênfigo/metabolismo , Estresse Oxidativo/fisiologia , Desmogleína 1/imunologia , Malondialdeído/sangue , Anticorpos/sangue , Peru , Valores de Referência , Remissão Espontânea , Ensaio de Imunoadsorção Enzimática , Peroxidação de Lipídeos/fisiologia , Estudos de Casos e Controles , Estudos Transversais , Estatísticas não Paramétricas , Doenças Endêmicas , Desmogleína 1/sangueRESUMO
OBJECTIVE: The aim of the present study was to investigate the association of the redox state via malondialdehyde (MDA) as a lipid peroxidation biomarker and hydrophilic antioxidant capacity (HAC) with dietary, anthropometric, demographic, socio-economic and clinical variables as well as the serum concentrations of vitamins in children aged 20-36 months. This cross-sectional study was conducted from May 2013 to May 2014 and included a total of 100 children. METHODS: The variables studied included anthropometric measurements, dietary intake by the Food Frequency Questionnaire (FFQ), socio-demographic features, clinical attributes, serum redox status, and serum vitamin concentrations. RESULTS: Children with a family income above the minimum wage and adequate body mass index (BMI) presented higher HAC. The MDA concentration was higher in children older than 24 months. Breastfeeding for up to 120 days provided greater antioxidant capacity. Children classified in the 2nd tertile for "fruit and vegetables" and "milk and dairy products" consumption showed lower levels of MDA. There was a positive correlation of MDA with serum vitamin A levels. These results show that among children in the 20-36 months age group, family income, breastfeeding, BMI and intake of fruits and vegetables can have an influence on the imbalance of the redox state. CONCLUSION: One strategy to prevent the imbalance between oxidants and antioxidants could be for health professionals to raise awareness among families, as such knowledge could repress/prevent the progression/initiation of several diseases in adult life.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Peroxidação de Lipídeos/efeitos dos fármacos , Estado Nutricional/fisiologia , Comportamento Alimentar/fisiologia , Antioxidantes/administração & dosagem , Oxirredução , Fatores Socioeconômicos , Peroxidação de Lipídeos/fisiologia , Estudos TransversaisRESUMO
ABSTRACT Purpose To determine enzymatic antioxidant and lipid peroxidation levels in seminal plasma of patients orchiectomized for testicular tumors. Materials and Methods The study included 52 patients: 26 control men and 26 orchiectomized patients for testicular tumor, of which 12 men had seminoma tumor and 14 men non-seminoma tumor. After semen analysis performed according to the WHO guidelines, an aliquot of semen was centrifuged and the seminal plasma was collected. Lipid peroxidation was performed by thiobarbituric acid reactive substances (TBARS) assay and antioxidant profile was assessed by analyzing catalase, glutathione peroxidase (GPx) and superoxide anion (SOD) activities using colorimetric assays with a standard spectrophotometer. Data were tested for normality and compared using one-way ANOVA (p<0.05). Results Seminoma and non-seminoma groups presented lower sperm concentration and morphology when compared to control group (p=0.0001). Both study groups (seminoma and non-seminoma) presented higher TBARS levels when compared to control group (p=0.0000013). No differences were observed for SOD (p=0.646) andGPx (p=0.328). It was not possible to access the enzymatic activity of catalase in any group. Conclusion Patients with testicular tumor present increased semen oxidative stress, but no differences were observed in antioxidant levels, even after orchiectomy. This indicates that most likely an increased generation of oxidative products takes place in these patients.
Assuntos
Humanos , Masculino , Adolescente , Adulto , Adulto Jovem , Sêmen/enzimologia , Neoplasias Testiculares/metabolismo , Peroxidação de Lipídeos/fisiologia , Seminoma/metabolismo , Antioxidantes/metabolismo , Oligospermia , Contagem de Espermatozoides , Superóxido Dismutase/metabolismo , Neoplasias Testiculares/cirurgia , Orquiectomia , Catalase/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Estresse Oxidativo/fisiologia , Análise do Sêmen , Glutationa Peroxidase/metabolismo , Pessoa de Meia-IdadeRESUMO
ABSTRACT Background Obesity is characterized by a deposition of abnormal or excessive fat in adipose tissue, and is linked with a risk of damage to several metabolic and pathological processes associated with oxidative stress. To date, salivary oxidative biomarkers have been minimally explored in obese individuals. Thus, the aim of this study was to assess the concentrations of salivary oxidative biomarkers (ferric-reducing antioxidant power, uric acid, sulfhydryl groups) and lipid peroxidation in obese and overweight young subjects. Materials and methods Levels of lipid peroxidation, ferric-reducing antioxidant power, uric acid, and SH groups were determined in the saliva and serum of 149 young adults, including 54 normal weight, 27 overweight, and 68 obese individuals. Anthropometric measurements were also evaluated. Results Salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, as well as serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation were higher in obese patients when compared with individuals with normal weight. There were correlations between salivary and serum ferric-reducing antioxidant power and salivary and serum uric acid in the obese and normal-weight groups. Conclusions Our results indicate that the increase in salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, and serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation could be related to the regulation of various processes in the adipose tissue. These findings may hold promise in identifying new oxidative markers to assist in diagnosing and monitoring overweight and obese patients.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Saliva/metabolismo , Saliva/química , Ácido Úrico/análise , Peroxidação de Lipídeos/fisiologia , Sobrepeso/sangue , Antioxidantes/análise , Obesidade/sangue , Oxirredução , Valores de Referência , Compostos de Sulfidrila/análise , Biomarcadores/análise , Estudos de Casos e Controles , Antropometria , Espécies Reativas de Oxigênio/metabolismo , Estatísticas não Paramétricas , Estresse Oxidativo/fisiologiaRESUMO
Summary Introduction: Obesity refers to the accumulation of fatty tissues and it favors the occurrence of oxidative stress. Alternatives that can contribute to body weight reduction have been investigated in order to reduce the production of reactive oxygen species responsible for tissue damage. The aim of the current study was to assess whether the oxidant and antioxidant markers of obese women before and after bariatric surgery were able to reduce oxidative damage. Method: We have assessed 16 morbidly obese women five days before and 180 days after the surgery. The control group comprised 16 non-obese women. Levels of thiobarbituric acid-reactive substances, carbonylated proteins, reduced glutathione and ascorbic acid were assessed in the patients' plasma. Results: Levels of lipid peroxidation and protein carbonylation in the pre-surgical obese women were higher than those of the controls and post-surgical obese women. Levels of reduced glutathione in the pre-surgical obese women were high compared to the controls, and declined after surgery. Levels of ascorbic acid fell in the pre--surgical obese women compared to the control and post-surgical obese women. Conclusion: Body weight influences the production of reactive oxygen species. Bariatric surgery, combined with weight loss and vitamin supplementation, reduces cellular oxidation, thus reducing tissue damage.
Resumo Introdução: Na obesidade, verifica-se um acúmulo de tecido adiposo, o que favorece a ocorrência de estresse oxidativo. A fim de diminuir a produção das espécies reativas que levam a danos teciduais, buscam-se alternativas que contribuam para a redução do peso corporal. Este estudo avaliou se os marcadores oxidantes e antioxidantes de obesas antes e após cirurgia bariátrica reduziram o dano oxidativo. Método: Foram avaliadas 16 mulheres obesas mórbidas cinco dias antes e 180 dias após o procedimento cirúrgico. O grupo controle constituiu-se de 16 mulheres não obesas. Os níveis das substâncias reativas ao ácido tiobarbitúrico, das proteínas carboniladas, da glutationa reduzida e do ácido ascórbico foram avaliados no plasma dessas pacientes. Resultados: Os níveis de lipoperoxidação e da carbonilação de proteínas nas obesas pré-cirúrgicas eram mais elevados quando comparados ao controle e às obesas pós-cirúrgicas; os níveis de glutationa reduzida eram maiores nas obesas pré-cirúrgicas em comparação ao controle e diminuíram após a cirurgia; os níveis de ácido ascórbico eram menores nas obesas pré-cirúrgicas em relação ao controle e às obesas pós-cirúrgicas. Conclusão: Observou-se que a massa corporal influenciou na produção das espécies reativas. A cirurgia bariátrica, somada à perda de peso e à suplementação vitamínica, diminui a oxidação celular e, com isso, reduz os danos teciduais.
Assuntos
Humanos , Feminino , Adulto , Estresse Oxidativo/fisiologia , Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Obesidade/metabolismo , Período Pós-Operatório , Ácido Ascórbico/sangue , Biomarcadores/sangue , Peroxidação de Lipídeos/fisiologia , Estudos de Casos e Controles , Análise de Variância , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Espécies Reativas de Oxigênio/sangue , Estatísticas não Paramétricas , Carbonilação Proteica/fisiologia , Glutationa/sangue , Pessoa de Meia-Idade , Antioxidantes/análiseRESUMO
Abstract Objetive: To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Methods: Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. Results: The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children (p <0.05). The circulating oxidized low density lipoprotein (p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro (p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma (p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95%: 1.016-1.179; p= 0.017) and Vitamin C (OR: 3.21, CI 95%: 1.104-9.938; p= 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. Conclusion: The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups.
Resumen Objetivo: Establecer la asociación entre la estratificación socioeconómica y marcadores plasmáticos de lipoperoxidación y antioxidantes en escolares venezolanos de clase media y en pobreza crítica. Métodos: Estudio transversal de 114 escolares con edades entre 7 y 9 años. Se determinó el estrato socioeconómico, la ingesta dietaria de macro y micronutrientes, peso, talla, perfil lipídico e indicadores plasmáticos de peroxidacion lipídica y antioxidantes enzimáticos y no-enzimáticos. Resultados: La ingesta dietaria promedio de energía, carbohidratos y vitamina A así como el porcentaje de energía obtenida de los carbohidratos fueron significativamente más elevados en los niños de clase media comparados con los niños en pobreza crítica (p <0.05). La concentración de lipoproteína de baja densidad oxidada circulante y la susceptibilidad de las lipoproteínas de baja densidad y muy baja densidad a la oxidación in vitro (p <0.05) fueron significativamente más elevadas en los niños de clase media, mientras los niños en pobreza crítica demostraron niveles plasmáticos de vitamin C y E significativamente más bajos (p <0.05). Las frecuencia de déficit de antioxidantes no enzimáticos fue elevada en ambos grupos estudiados. Las concentraciones de lipoproteína de baja densidad oxidada circulante (OR: 1.09, IC 95%: 1.016-1.179; p= 0.017) y vitamina C (OR: 3.21, IC 95%: 1.104-9.938; p= 0.032) se asociaron significativamente al estrato socioeconómico independientemente del sexo, historia familiar de enfermedad coronaria prematura, triglicéridos, ingesta dietaria de vitaminas C y E y contaje total de glóbulos blancos. Conclusión: La estratificación socioeconómica se asoció a las concentraciones de lipoproteína de baja densidad oxidada circulante y vitamina C en escolares venezolanos, los resultados sugirieron la necesidad de mejorar la ingesta dietaria de antioxidantes en ambos estratos socioeconómicos estudiados.
Assuntos
Criança , Feminino , Humanos , Masculino , Pobreza , Peroxidação de Lipídeos/fisiologia , Comportamento Alimentar/fisiologia , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Fatores Socioeconômicos , Venezuela , Estudos Transversais , Lipoproteínas LDL/sangue , Antioxidantes/administração & dosagemRESUMO
ABSTRACT Objective The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Materials and methods Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Results Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. Conclusion This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.
Assuntos
Animais , Masculino , Estresse Oxidativo/fisiologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Peróxidos/urina , Glicemia/análise , Peso Corporal/fisiologia , Peroxidação de Lipídeos/fisiologia , Ratos Wistar , Estreptozocina , Creatinina/análise , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/induzido quimicamente , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/patologia , Albuminúria/urina , Modelos Animais de Doenças , Taxa de Filtração Glomerular/fisiologia , Rim/metabolismo , Rim/patologiaRESUMO
Abstract Background: Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective: We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method: Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results: Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion: Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.
Resumo Fundamentos: A doença arterial coronariana é duas a três vezes mais comum em indivíduos diabéticos. O nitrato/nitrito dietético tem efeitos benéficos tanto para o diabetes quanto para a doença cardiovascular, assim como efeitos protetores contra a lesão de isquemia-reperfusão (IR) miocárdica em animais saudáveis. Porém, os efeitos do nitrato na lesão de IR miocárdica em ratos diabéticos ainda não foram investigados. Objetivos: Foram examinados os efeitos sobre a lesão de IR miocárdica da adição de nitrato à dieta de ratos com diabetes mellitus tipo 2 induzido por estreptozotocina-nicotinamida. Métodos: Os ratos foram divididos em quatro grupos (n = 7 em cada grupo): controle, controle+nitrato, diabetes e diabetes+nitrato. O diabetes foi induzido nos animais por injeção de estreptozotocina e nicotinamida. Nitrato (nitrato de sódio) foi adicionado à água de beber (100 mg/L) por 2 meses. Os corações foram perfundidos em sistema de Langendorff aos 2 meses e avaliados antes (basal) e após IR miocárdica em relação aos seguintes parâmetros: pressão desenvolvida no ventrículo esquerdo (PDVE), taxas máximas de variação positiva e negativa da pressão ventricular esquerda (±dP/dt), expressão do RNAm da óxido nítrico (NO) sintase (NOS) endotelial (eNOS) e da NOS induzível (iNOS), além de níveis de malondialdeído (MDA) e metabólitos do óxido nítrico (NOx). Resultados: A recuperação da PDVE e ±dP/dt foi inferior nos ratos diabéticos versus controles, mas quase normalizou após ingestão de nitrato. Ratos diabéticos apresentaram expressão diminuída de eNOS e aumentada de iNOS tanto no estado basal quanto após IR, e o consumo dietético de nitrato restaurou estes valores para o estado normal após a IR. O nível de NOx cardíaco foi menor nos ratos diabéticos em comparação aos controles no momento basal, mas foi superior após a IR. Ratos diabéticos apresentaram níveis mais elevados de MDA tanto no estado basal quanto após IR que, juntamente com os níveis cardíacos de NOx, reduziram após consumo dietético do nitrato. Conclusões: O consumo dietético de nitrato por ratos diabéticos ofereceu cardioproteção contra a lesão de IR através da regulação da expressão de eNOS e iNOS e inibição da peroxidação lipídica no coração.
Assuntos
Animais , Masculino , Cardiotônicos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Isquemia Miocárdica/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Nitratos/uso terapêutico , Peroxidação de Lipídeos/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Reprodutibilidade dos Testes , Resultado do Tratamento , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/metabolismo , Estreptozocina , Vasos Coronários/fisiopatologia , Vasos Coronários/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Hemodinâmica , Malondialdeído/análiseRESUMO
Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Citocinas/sangue , Hipertensão/fisiopatologia , Pressão Arterial/fisiologia , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Frequência Cardíaca/fisiologia , Temperatura Alta , Hipertensão/sangue , Inflamação/fisiopatologia , Peroxidação de Lipídeos/fisiologia , Oxirredução , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Although it is well known that physical training ameliorates brain oxidative function after injuries by enhancing the levels of neurotrophic factors and oxidative status, there is little evidence addressing the influence of exercise training itself on brain oxidative damage and data is conflicting. This study investigated the effect of well-established swimming training protocol on lipid peroxidation and components of antioxidant system in the rat brain. Male Wistar rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8) and non-trained (n=7) groups. Forty-eight hours after the last session of exercise, animals were euthanized and the brain was collected for oxidative stress analysis. Swimming training decreased thiobarbituric acid reactive substances (TBARS) levels (P<0.05) and increased the activity of the antioxidant enzyme superoxide dismutase (SOD) (P<0.05) with no effect on brain non-enzymatic total antioxidant capacity, estimated by FRAP (ferric-reducing antioxidant power) assay (P>0.05). Moreover, the swimming training promoted metabolic adaptations, such as increased maximal workload capacity (P<0.05) and maintenance of body weight. In this context, the reduced TBARS content and increased SOD antioxidant activity induced by 8 weeks of swimming training are key factors in promoting brain resistance. In conclusion, swimming training attenuated oxidative damage and increased enzymatic antioxidant but not non-enzymatic status in the rat brain.
Assuntos
Animais , Masculino , Condicionamento Físico Animal/fisiologia , Natação/fisiologia , Encéfalo/metabolismo , Estresse Oxidativo/fisiologia , Terapia por Exercício/métodos , Antioxidantes/metabolismo , Valores de Referência , Espectrofotometria , Superóxido Dismutase/análise , Fatores de Tempo , Peso Corporal , Peroxidação de Lipídeos/fisiologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Espécies Reativas de Oxigênio/metabolismo , Malondialdeído/análise , Malondialdeído/metabolismo , Antioxidantes/análiseRESUMO
Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g) underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10−12-10−4 M) and contraction in response to phenylephrine (10−12-10−5 M) were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20), G4 (7.8±0.29), and G5 (7.9±0.21), compared to the control group (7.2±0.04), while relaxation in the G6 (7.4±0.25) and G8 (7.0±0.06) groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1) and G8 (9.7±0.29) compared to the control (7.1±0.1), G3 (7.3±0.2), G4 (7.2±0.1) and G5 (7.2±0.2%) groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA). These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation.
Assuntos
Animais , Masculino , Aorta/fisiologia , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Esforço Físico/fisiologia , Vasodilatação/fisiologia , Análise de Variância , Aorta/metabolismo , Teste de Esforço , Coração/fisiologia , Contração Isométrica/fisiologia , Ácido Láctico/sangue , Malondialdeído/análise , Ratos Wistar , Natação/fisiologiaRESUMO
Objective: Our objective was to systematically review the published observational research related to the role of oxidative-nitrosative stress in pathogenesis of dengue. Methods: We searched electronic databases (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) using the term: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide, and nitric oxide synthase. Articles were selected for review by title and abstract excluding letter, review, in vivo and in vitro studies, and duplicates studies. Selected articles were reviewed for study design, original purposes, sample size, main outcomes, methods, and oxidative-nitrosative stress markers values. Results: In total, 4,331 non-duplicates articles were identified from electronic databases searches, of which 16 were eligible for full text searching. Data from the observational studies originate from Asian countries (50%; 8/16), South American countries (31.2%; 5/16), and Central America and the Caribbean countries (18.8%; 3/16). Case-control study was the type of design most common in researches reviewed. The 1997 World Health Organization (WHO) dengue case classification criteria were used in all studies included in this review. Conclusions: Based on published data found in peer-reviewed literature, oxidative and nitrosative stress are demonstrated by changes in plasma levels of nitric oxide, antioxidants, lipid peroxidation and protein oxidation markers in patients with dengue infection. Additionally, elevated serum protein carbonyls and malondialdehyde levels appear to be associated with dengue disease severity.
Objetivo: Sistematizar las evidencias observacionales sobre la relación entre el estrés oxidativo-nitrosativo y la patogénesis del dengue. Métodos: Revisión sistemática de estudios observacionales en las bases de datos (PubMed, EMBASE, The COCHRANE library, ScienceDirect, Scopus, SciELO, LILACS via Virtual Health Library, Google Scholar) utilizando las siguientes palabras clave: dengue, dengue virus, severe dengue, oxidative stress, nitrosative stress, antioxidants, oxidants, free radicals, oxidized lipid products, lipid peroxides, nitric oxide y nitric oxide synthase. La selección inicial fue realizada a partir del título y resumen excluyéndose: cartas para editor, revisiones, estudios in vivo/in vitro y duplicados. A cada artículo seleccionado, se le revisó el diseño del estudio, objetivo, tamaño de la muestra, resultados principales y niveles plasmáticos de los marcadores de estrés oxidativo-nitrosativo. Resultados: De 4,331 publicaciones encontradas, 16 estudios cumplieron con los criterios de inclusión. El 50% (8/16) de los estudios revisados fueron realizados en países de Sur América, Centro América y del Caribe. El diseño de casos y controles fue el más frecuente. El anterior sistema de clasificación de casos (OMS-1997) fue utilizado en todos los estudios incluidos en esta revisión. Conclusiones: El estrés oxidativo-nitrosativo se encuentra presente en el curso de la infección por virus dengue, demostrado por los cambios en las concentraciones plasmáticas de óxido nítrico, antioxidantes y marcadores de lipoperoxidación y de oxidación de proteínas. Por último, parece existir una asociación entre la elevación de los niveles plasmáticos de los carbonilos proteicos y malondialdehído con la severidad del dengue.