Application of mixture analysis methods in association between metals mixture exposure and DNA oxidative damage / 中华预防医学杂志

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.

Oxidative stress in maternal milk and cord blood in gestational diabetes mellitus: a prospective study

ABSTRACT BACKGROUND: Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. OBJECTIVE: Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). DESIGN AND SETTING: Prospective study at a university hospital in Turkey. METHODS: The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. RESULTS: No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. CONCLUSION: Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.

4-hydroxy-2-nonenal as a marker of the oxidative stress in brains of dogs with canine distemper / 4-hidroxi-2-nonenal como marcador de estresse oxidativo no cérebro de cães com cinomose

Canine Distemper is a disease caused by Canine morbillivirus (CM), a pantropic virus that can affect the central nervous system (CNS), causing demyelination. However, the pathogenesis of this lesion remains to be clarified. Brain samples of 14 naturally infected dogs by CM were analyzed to evaluate the presence of oxidative stress and demyelination. RT-PCR assay was performed to confirm a diagnosis of canine distemper in the brain, immunohistochemistry anti-CM was used to localize the viral proteins in the tissue, and anti-4-hydroxy-2-nonenal (4-HNE) was a marker of a product of lipid peroxidation. The results showed the presence of viral proteins in the demyelinated area with the presence of 4-HNE. Our results suggest that the CM virus infection causes oxidative stress leading to lipid peroxidation, which causes tissue damage and demyelination. In conclusion, oxidative stress plays a significant role in canine distemper pathogenesis in the CNS.(AU)

A cinomose canina é uma doença causada pelo Morbilivírus canino (CM), um vírus pantrópico que pode afetar o sistema nervoso central (SNC), causando desmielinização. No entanto, a patogênese dessa lesão não está totalmente esclarecida. RT-PCR e imuno-histoquímica foram realizadas para confirmação do diagnóstico de cinomose em amostras de encéfalo de 14 cães naturalmente infectados. Após confirmação, foi realizada uma avaliação do estresse oxidativo por imuno-histoquímica com uso de anti-4-hidroxi-nonenal (4HNE) como marcador de produtos resultantes da peroxidação lipídica. Os resultados sugerem que a infecção pelo CM causa estresse oxidativo no tecido, levando a peroxidação lipídica, a qual causa danos ao tecido, culminando com desmielinização. Conclui-se que o estresse oxidativo tem papel importante na patogênese da cinomose canina no sistema nervoso central.(AU)

Short-term hiit does not promote oxidative stress or muscle damage / Hiit de corto plazo no promueve estrés oxidativo o daños musculares / Hiit de curto prazo não promove estresse oxidativo ou danos musculares

ABSTRACT Introduction: High intensity interval training (HIIT) is a method that is widely used today. Objective: The present study aimed to evaluate the effects of HIIT on markers of oxidative stress and muscle damage in rats. Methods: The sample consisted of 60-day-old Wistar rats, divided into two groups: a control group (n=8) and an HIIT group (n=8). The training consisted of fourteen 20-second swimming sessions (loaded with weights equivalent to 14% of their body weight) with 10-second intervals between each session, performed for 12 consecutive days. Results: HIIT induced a reduction (−17.75%) in thiobarbituric acid reactive substances (an oxidative stress marker) in hepatic tissue (p=0.0482). There was also a reduction (−31.80%) in the HIIT group in the level of superoxide dismutase enzyme activity in the liver (p=0.0375). However, there were no differences between the groups in catalase, glutathione peroxidase, glutathione reductase, the total content of SH sulfhydryls, hydroperoxides, or carbonylated proteins in the hepatic tissue. No significant differences were found in any of these markers in the gastrocnemius muscle. The muscle damage markers creatinine kinase and lactate dehydrogenase were also similar between the groups in the gastrocnemius. Conclusion: The conclusion was that that short-term HIIT does not cause oxidative stress or muscle damage. Level of evidence I; High-quality randomized clinical trial with or without statistically significant difference, but with narrow confidence intervals.

RESUMEN Introducción: El entrenamiento en intervalos de alta intensidad (HIIT) es un método muy utilizado actualmente. Objetivo: El presente estudio tuvo como objetivo evaluar los efectos del HIIT en corto plazo sobre marcadores de estrés oxidativo y daño muscular en ratones. Métodos: La muestra consistió en ratones Wistar con 60 días de edad, divididos en dos grupos: grupo control (n = 8) y grupo HIIT (n = 8). El entrenamiento consistió en catorce sesiones de natación de 20 segundos (con cargas equivalentes a 14% del peso corporal) con intervalos de 10 segundos entre cada sesión, realizadas durante 12 días consecutivos. Resultados: El HIIT indujo una reducción (-17,75%) de las sustancias reactivas al ácido tiobarbitúrico (un marcador de estrés oxidativo) en el tejido hepático (p = 0,0482). También hubo reducción (~31,80%) en el grupo HIIT en el nivel de enzima superóxido dismutasa en el hígado (p=0,0375). Sin embargo, no hubo diferencias entre los grupos con relación a catalasa, glutatión peroxidasa, glutatión reductasa, tenor total de sulfhidrilos SH, hidroperóxidos o proteínas carboniladas en el tejido hepático. No fue encontrada ninguna diferencia significativa en ninguno de esos marcadores en el músculo gastrocnemio. Los marcadores de lesión muscular, creatinina quinasa y lactato deshidrogenasa también fueron similares entre los grupos en el gastrocnemio. Conclusión: Fue posible concluir que el HIIT de corta duración no causa estrés oxidativo o daño muscular. Nivel de evidencia I; Estudio clínico aleatorizado de alta calidad con o sin diferencia estadísticamente significativa, pero con intervalos de información estrechos.

RESUMO Introdução: O treinamento intervalado de alta intensidade (HIIT) é um método muito utilizado atualmente. Objetivo: O presente estudo objetivou avaliar os efeitos do HIIT em curto prazo sobre marcadores de estresse oxidativo e dano muscular em ratos. Métodos: A amostra consistiu em ratos Wistar com 60 dias de idade, divididos em dois grupos: grupo controle (n = 8) e grupo HIIT (n = 8). O treinamento consistiu em quatorze sessões de natação de 20 segundos (com cargas equivalentes a 14% do peso corporal) com intervalos de 10 segundos entre cada sessão, realizadas por 12 dias consecutivos. Resultados: O HIIT induziu uma redução (-17,75%) das substâncias reativas ao ácido tiobarbitúrico (um marcador de estresse oxidativo) no tecido hepático (p = 0,0482). Houve também redução (-31,80%) no grupo HIIT no nível de enzima superóxido dismutase no fígado (p = 0,0375). No entanto, não houve diferenças entre os grupos com relação a catalase, glutationa peroxidase, glutationa redutase, teor total de sulfidrilas SH, hidroperóxidos ou proteínas carboniladas no tecido hepático. Nenhuma diferença significativa foi encontrada em qualquer um desses mascadores no músculo gastrocnêmio. Os marcadores de lesão muscular, creatinina quinase e lactato desidrogenase, também foram semelhantes entre os grupos no gastrocnêmio. Conclusão: Foi possível concluir que o HIIT de curta duração não causa estresse oxidativo ou dano muscular. Nível de evidência I; Estudo clínico randomizado de alta qualidade com ou sem diferença estatisticamente significante, mas com intervalos de informação estreitos.

Characterization of oxidative stress in animal model of neonatal hypoxia

Purpose To evaluate the oxidative stress in swine neonates submitted to hypoxia. Methods Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. Results 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets’ brain tissue were analyzed. Conclusions Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.

Ácido úrico y gamma-glutamiltransferasa como biomarcadores de enfermedad cardiovascular a través del estrés oxidativo / Uric acid and gamma-glutamyltransferase as biomarkers of cardiovascular disease via oxidative stress

Introducción: Las enfermedades cardiovasculares constituyen la principal causa de mortalidad y morbilidad a nivel mundial. Reconocidas como problemas de salud de impacto social, han motivado a muchos científicos a tratar de explicar su patogénesis. Actualmente se plantea de la existencia de otros factores de riesgo, independientemente de los clásicos. Entre estos factores se describen el papel de las altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre, biomarcadores de estrés oxidativo. Estos elementos que de manera individual pudieran contribuir a las enfermedades cardiovasculares, parecen tener un efecto sinérgico. Objetivo: Revisar las evidencias que sostienen que altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre pueden constituir factores de riesgo que desde el estrés oxidativo contribuyan a las enfermedades cardiovasculares. Métodos: Se recopiló la información a partir de las bases de datos de diferentes buscadores (Medline-Pubmed, Cochrane, Scopus y SciELO) entre el 1 de marzo del 2019 y el 23 de mayo 2020. Conclusiones: Se encontró que, tanto el ácido úrico como la gamma-glutamiltransferasa son productos horméticos que a bajas concentraciones tienen efecto antioxidante en el organismo, pero al elevarse involucran la ocurrencia de procesos oxidativos que conducen a la disfunción endotelial y las enfermedades cardiovasculares(AU)

Introduction: Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. Recognized as a health problem of social impact; they have prompted many scientists to try to explain their pathogenesis. New risk factors are currently acknowledged alongside the classic ones. These factors include the role of high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood, both of which are biomarkers of oxidative stress. These elements may individually contribute to the development of cardiovascular diseases, and seem to have a synergistic effect. Objective: Review the evidence supporting the idea that high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood may be risk factors contributing to the development of cardiovascular diseases via oxidative stress. Methods: Data were collected from the databases of various search engines (Medline-Pubmed, Cochrane, Scopus and SciELO) from 1 March 2019 to 23 May 2020. Conclusions: It was found that uric acid and gamma-glutamyltransferase are hormetic products causing an antioxidant effect on the organism at low concentrations. However, when concentrations rise, they are involved in the occurrence of oxidative processes leading to endothelial dysfunction and cardiovascular diseases(AU)

Ischemia-modified albumin as a possible marker of oxidative stress in patients with telogen effluvium

Abstract Background Telogen effluvium is the most common form of non-scarring alopecia characterized by diffuse hair loss. Ischemia-modified albumin is a marker of oxidative stress and inflammation. Objective The aim of this study was to compare the levels of ischemia-modified albumin of telogen effluvium patients with healthy controls. Methods Ninety-one patients diagnosed with telogen effluvium and 35 healthy volunteers were included in the study. Serum ischemia-modified albumin level was determined by a fast-colorimetric method, and albumin cobalt binding test. The results were evaluated statistically. Results There was no statistically significant difference between the serum albumin values of patient and control groups (p = 0.739). Serum ischemia-modified albumin values were significantly higher in the patients with telogen effluvium than healthy controls (p < 0.001). Study limitations Body mass index values of the patient and control groups could not be calculated. Conclusions To the best of the authors' knowledge, this is the first clinical study to investigate the role of oxidative stress in the pathogenesis of telogen effluvium using ischemia-modified albumin as a biomarker. Based on the results of the present study, it can be considered that oxidative stress plays an important role in the pathogenesis of telogen effluvium. There is a need for further studies to support the results of this study, to demonstrate the possible effects of oxidative stress, and to investigate the other oxidative stress markers in the pathogenesis of telogen effluvium.

Efectos biológicos protectores del ejercicio en modelos experimentales de tabaquismo: más allá de la cesación y la abstinencia / Protectives biological effects of exercise in animals models of tobacco smoking: beyond tobacco cessation and withdrawal

El tabaquismo es considerado una de las principales causas de morbilidad y mortalidad en la población general. En Chile la prevalencia de tabaquismo alcanza el 36,7% en hombres y 28,5% en mujeres. En este contexto, diversas estrategias farmacológicas y no farmacológicas han sido propuestas para promover la cesación de su consumo, así como para contrarrestar las comorbilidades asociadas al tabaquismo prolongado. Entre ellas, el ejercicio físico ha sido tradicionalmente considerado, por su impacto en la promoción de la cesación del hábito tabáquico, así como también por sus efectos en la reducción de las manifestaciones clínicas del síndrome de abstinencia post cesación. No obstante, estudios realizados en modelos animales durante los últimos 10 años han proporcionado datos contundentes para sustentar la hipótesis de que la práctica regular de ejercicio físico sería también efectiva para prevenir o modular el estrés oxidativo y la respuesta inflamatoria inducida por el tabaco, previniendo el deterioro orgánico de los sistemas fisiológicos expuestos. Esta revisión tiene por objetivo discutir la evidencia publicada respecto a los efectos biológicos inducidos por ejercicio físico y su impacto en la reversión de los mecanismos fisiopatológicos que subyacen a las comorbilidades asociadas al hábito tabáquico, focalizando el análisis en los mecanismos de estrés oxidativo y respuesta inflamatoria del sistema respiratorio y cardiovascular.

Smoking is considered one of the main causes of morbidity and mortality in the general population. In Chile, the prevalence of smoking reaches 36.7% in men and 28.5% in women. In this context, several pharmacological and non-pharmacological strategies have been proposed to promote the cessation of their use, as well as to counteract the comorbidities associated with prolonged smoking. Among them, physical exercise has been traditionally considered, due to its impact on the promotion of cessation of smoking, as well as its effects in reducing the clinical manifestations of withdrawal syndrome. However, studies conducted in animal models during the last 10 years have provided strong data to support the hypothesis that regular practice of physical exercise would also be effective in preventing or modulating oxidative stress and the inflammatory response induced by tobacco, preventing the organic deterioration of exposed physiological systems. The objective of this review is to discuss the published evidence regarding the biological effects induced by physical exercise and its impact on the reversion of the pathophysiological mechanisms underlying the comorbidities associated with smoking, focusing the analysis on the mechanisms of oxidative stress and inflammatory response of the respiratory and cardiovascular system.

Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Effects of Physical Training on the Myocardium of Oxariectomized LDLr Knockout Mice: MMP 2/9, Collagen I/III, Inflammation and Oxidative Stress / Efeitos do Treinamento Físico sobre o Miocárdio de Camundongos LDLr Knockout Ovariectomizadas: MMP-2 e -9, Colágeno I/III, Inflamação e Estresse Oxidativo

Abstract Background: The emergence of coronary heart disease is increased with menopause, physical inactivity and with dyslipidemia. Physical training is known to promote the improvement of cardiovascular functions. Objective: To investigate the effects of aerobic physical training on the left ventricle in ovariectomized LDL knockout mice. Methods: Thirty animals were divided into 6 groups (n = 5): Sedentary non-ovariectomized control; Sedentary ovariectomized control; Trained ovariectomized control; Sedentary non-ovariectomized LDL-knockout, sedentary ovariectomized LDL-knockout and trained ovariectomized LDL-knockout. We analyzed the average parameters of apparent density of collagen fibers types I and III, and metalloproteinase type 2 and type 9, were considered significant p < 0.05. Results: The results showed that the proposed exercise protocol altered the volume of type I collagen fibers, altered collagen remodeling parameters (MMP-2), and also reduced the 8-hydroxy-2'-deoxyguanosine (8OHdG) oxidative stress parameter. Conclusion: Moderate intensity aerobic training acts on collagen fiber volume, on collagen remodeling with the reduction of oxidative stress in the left ventricles of ovariectomized LDL-knockout mice.

Resumo Fundamento: O surgimento da doença cardíaca coronariana aumenta com a menopausa, inatividade física e dislipidemia. Sabe-se que o treinamento físico promove a melhora das funções cardiovasculares Objectivo: Investigar os efeitos do treinamento físico aeróbico sobre o ventrículo esquerdo em camundongos LDL knockout ovariectomizadas. Métodos: Trinta animais foram divididos em 6 grupos (n = 5): controle sedentário não ovariectomizado, controle sedentário ovariectomizado, controle treinado ovariectomizado, sedentário LDL-knockout não ovariectomizado, sedentário LDL-knockout ovariectomizado e treinado LDL-knockout ovariectomizado. Analisamos os parâmetros médios da densidade de volume de fibras colágenas tipo I e III, e metaloproteinases 2 e 9. Valores de p < 0,05 foram considerados significativos. Resultados: Os resultados mostram que o protocolo de exercício proposto alterou o volume de fibras colágenas do tipo I e os parâmetros de remodelamento do colágeno (MMP-2), e ainda reduziu o parâmetro de estresse oxidativo do 8-hidroxi-2'-deoxiganosina (8-OhdG). Conclusão: O treinamento aeróbico de intensidade moderada age sobre o volume das fibras colágenas e sobre o remodelamento de colágeno, com redução do estresse oxidativo em ventrículos esquerdos de camundongos ovariectomizados LDLr Knockout.

Euterpe Oleracea Mart. (Açaí) Reduces Oxidative Stress and Improves Energetic Metabolism in Myocardial Ischemia-Reperfusion Injury in Rats / Euterpe Oleracea Mart. (Açaí) Reduz o Estresse Oxidativo e Melhora o Metabolismo Energético da Lesão de Isquemia-Reperfusão Miocárdica Em Ratos

Abstract Background: Euterpe oleracea Mart. (açaí) is a fruit with high antioxidant capacity and could be an adjuvant strategy to attenuate ischemia-reperfusion injury. Objective: To evaluate the influence of açaí in global ischemia-reperfusion model in rats. Methods: Wistar rats were assigned to 2 groups: Control (C: receiving standard chow; n = 9) and Açaí (A: receiving standard chow supplemented with 5% açaí; n = 10). After six weeks, the animals were subjected to the global ischemia-reperfusion protocol and an isolated heart study to evaluate left ventricular function. Level of significance adopted: 5%. Results: There was no difference between the groups in initial body weight, final body weight and daily feed intake. Group A presented lower lipid hydroperoxide myocardial concentration and higher catalase activity, superoxide dismutase and glutathione peroxidase than group C. We also observed increased myocardial activity of b-hydroxyacyl coenzyme-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase in the A group as well as lower activity of the lactate dehydrogenase and phosphofructokinase enzymes. The systolic function was similar between the groups, and the A group presented poorer diastolic function than the C group. We did not observe any difference between the groups in relation to myocardial infarction area, total and phosphorylated NF-kB, total and acetylated FOXO1, SIRT1 and Nrf-2 protein expression. Conclusion: despite improving energy metabolism and attenuating oxidative stress, açai supplementation did not decrease the infarcted area or improve left ventricular function in the global ischemia-reperfusion model.

Resumo Fundamento: Euterpe oleracea Mart. (açaí) é uma fruta com alta capacidade antioxidante e pode ser uma estratégia adjuvante para atenuar a lesão de isquemia-reperfusão. Objetivo: Avaliar a influência do açaí no modelo global de isquemia-reperfusão em ratos. Metodologia: Ratos Wistar foram divididos em 2 grupos: Controle (C: recebendo ração padrão; n = 9) e Açaí (A: recebendo ração padrão suplementada com 5% de açaí; n = 10). Após seis semanas, os animais foram submetidos ao protocolo global de isquemia-reperfusão e a estudo do coração isolado para avaliar a função ventricular esquerda. Nível de significância adotado: 5%. Resultados: Não houve diferença entre os grupos quanto ao peso corporal inicial e final, e a ingestão diária de ração. O grupo A apresentou menor concentração miocárdica de hidroperóxido lipídico e maior atividade de catalase, superóxido dismutase e glutationa peroxidase do que o grupo C. Também observamos aumento da atividade miocárdica da b-hidroxiacil coenzima-A desidrogenase, piruvato desidrogenase, citrato sintase, complexo I, complexo II e ATP sintase no grupo A, bem como menor atividade das enzimas lactato desidrogenase e fosfofructoquinase. A função sistólica foi semelhante entre os grupos, e o grupo A apresentou função diastólica pior que C. Não foram observadas diferenças entre os grupos em relação à área de infarto do miocárdio, e expressão proteica de NF-kB total e fosforilado, e das proteínas FOXO1, SIRT1 e Nrf-2. Conclusão: apesar de melhorar o metabolismo energético e atenuar o estresse oxidativo, a suplementação de açaí não diminuiu a área infartada nem melhorou a função ventricular esquerda no modelo global de isquemia-reperfusão.

Correlation between nutritional assessment and oxidative stress in candidates for liver transplant / Correlação entre avaliação nutricional e estresse oxidativo em candidatos ao transplante hepático

ABSTRACT Objective To evaluate the oxidative profile, nutritional status and food intake (caloric value; macronutrients; vitamins A, E and C; and zinc), and to correlate oxidative stress with nutritional status in patients who were candidates for liver transplant. Methods This is a cross-sectional, analytical, and descriptive study with 51 candidates for liver transplant. Sociodemographic and clinical data, anthropometric parameters, food consumption, and a 10mL blood sample were collected from each patient. Oxidative stress was analyzed by the thiobarbituric acid method. The consumption of macronutrients, caloric value and micronutrients (zinc, vitamins A, E and C) were qualitatively analyzed, and zinc was also quantitatively analyzed. Results The mean age was 49.17±8.17 years. The highest percentage of malnutrition was according to arm muscle circumference (56.86%), followed by arm circumference (52.94%), triceps skin fold (50.98%), and body mass index (1.96%). The mean malondialdehyde level was 14.80±8.72μM/L, presenting a negative correlation with the body mass index for patients with liver cirrhosis according to IMC-Campillo values (p=0.001; r=-0.430). Low energy, carbohydrate, protein, vitamin A and E consumption were observed in more than 50% of subjects. Conclusion This study showed an association of nutritional status through body mass index for patients with liver cirrhosis according to IMC-Campillo, with oxidative stress in patients with liver cirrhosis on a liver transplant waiting list.

RESUMO Objetivo Avaliar o perfil oxidativo, o estado nutricional e o consumo alimentar (valor calórico; macronutrientes; vitaminas A, E e C; e zinco), e correlacionar o estresse oxidativo com o estado nutricional em pacientes candidatos ao transplante hepático. Métodos Trata-se de estudo transversal, analítico e descritivo com 51 pacientes candidatos ao transplante hepático. Coletaram-se dados sociodemográficos e clínicos, parâmetros antropométricos, consumo alimentar e amostra de 10mL de sangue de cada paciente. O estresse oxidativo foi analisado por método do ácido tiobarbitúrico. O consumo de macronutrientes, do valor calórico e dos micronutrientes (zinco, vitaminas A, E e C) foi analisado qualitativamente, e o zinco também foi analisado quantitativamente. Resultados A média de idade foi de 49,17±8,17 anos. Maior percentual de desnutrição esteve de acordo com circunferência muscular do braço (56,86%), seguida de circunferência do braço (52,94%), dobra cutânea triciptal (50,98%) e índice de massa corporal (1,96%). A média do malondialdeído foi de 14,80±8,72µM/L, apresentando correlação negativa com os valores do índice de massa corporal para pacientes com cirrose hepática segundo IMC-Campillo (p=0,001; r=-0,430). Observou-se baixo consumo de energia, carboidrato, proteína, e vitaminas A e E em mais de 50% dos indivíduos. Conclusão Este estudo mostrou associação do estado nutricional, por meio do índice de massa corporal para pacientes com cirrose hepática segundo IMC-Campillo, com o estresse oxidativo em paciente com cirrose hepática em lista de transplante de fígado.

The heterologous expression of Escherichia coli MutT enzyme is involved in the protection against oxidative stress in Leishmania braziliensis

BACKGROUND Oxidative stress is responsible for generating DNA lesions and the 8-oxoguanine (8-oxoG) is the most commonly lesion found in DNA damage. When this base is incorporated during DNA replication, it could generate double-strand DNA breaks and cellular death. MutT enzyme hydrolyzes the 8-oxoG from the nucleotide pool, preventing its incorporation during DNA replication. OBJECTIVES To investigate the importance of 8-oxoG in Leishmania infantum and L. braziliensis, in this study we analysed the impact of heterologous expression of Escherichia coli MutT (EcMutT) enzyme in drug-resistance phenotype and defense against oxidative stress. METHODS Comparative analysis of L. braziliensis and L. infantum H2O2 tolerance and cell cycle profile were performed. Lines of L. braziliensis and L. infantum expressing EcMutT were generated and evaluated using susceptibility tests to H2O2 and SbIII, cell cycle analysis, γH2A western blotting, and BrdU native detection assay. FINDINGS Comparative analysis of tolerance to oxidative stress generated by H2O2 showed that L. infantum is more tolerant to exogenous H2O2 than L. braziliensis. In addition, cell cycle analysis showed that L. infantum, after treatment with H2O2, remains in G1 phase, returning to its normal growth rate after 72 h. In contrast, after treatment with H2O2, L. braziliensis parasites continue to move to the next stages of the cell cycle. Expression of the E. coli MutT gene in L. braziliensis and L. infantum does not interfere in parasite growth or in susceptibility to SbIII. Interestingly, we observed that L. braziliensis EcMutT-expressing clones were more tolerant to H2O2 treatment, presented lower activation of γH2A, a biomarker of genotoxic stress, and lower replication stress than its parental non-transfected parasites. In contrast, the EcMutT is not involved in protection against oxidative stress generated by H2O2 in L. infantum. MAIN CONCLUSIONS Our results showed that 8-oxoG clearance in L. braziliensis is important to avoid misincorporation during DNA replication after oxidative stress generated by H2O2.

Aging and low-intensity exercise change oxidative biomarkers in brain regions and radiographic measures of femur of Wistar rats

We investigated changes in oxidative biomarkers in brain regions such as brainstem, cerebellum, and cerebral cortex of 3-, 6-, 18-, 24-, and 30-month-old rats. We also assessed the effects of low-intensity exercise on these biomarkers in these regions of 6-, 18-, and 24-month-old rats that started exercise on a treadmill at 3, 15, and 21 months of age, respectively. Radiographic images of the femur were taken for all rats. A total of 25 rats (age: twelve 6-, ten 18-, ten 24-, and three 30-month-old rats) were used. Lipid hydroperoxide levels increased in cerebellum at 18 months. Total antioxidant activity exhibited lowest values in brainstem at 3 months. Superoxide dismutase activity did not exhibit significant changes during aging. Total thiol content exhibited lowest values in brain regions of 24- and 30-month-old rats. Exercise reduced total thiol content in brainstem at 6 months, but no change occurred in other regions and other ages. Femur increased its length and width and cortical thickness with advancing age. No change occurred in medullary width. Radiolucency increased and sclerosis was found in cortical and medullary bone with advancing age. Exercise reduced radiolucency and medullary sclerosis. Therefore, aging differentially changed oxidative biomarkers in different brain regions and radiographic measures of the femur. Low-intensity exercise only ameliorated some radiographic measurements of femur. Since the present study possessed limitations (small number of rats per group), a beneficial effect of regular low-intensity exercise on oxidative markers in brain cannot be ruled out.

Physical activity impact on motor development and oxidative stress biomarkers in school children with intellectual disability

SUMMARY OBJECTIVE Lower physical fitness and poor motor performance were shown to be linked with higher levels of oxidative stress in children and adolescents with intellectual disabilities. Therefore, a moderate aerobic exercise for 12-weeks was performed to evaluate the effects of physical activity scores on motor functions, oxidative stress, and intelligence quotients (IQ) in school children with intellectual disability. METHODS A total of 65 school children aged (12-18 Yrs) were randomly included in this study. Intellectual disability (ID),motor skills,physical fitness(VO2max), total energy expenditure (TEE), MDA, 8-OHdG, TAC, NO, and total oxidative stress(OS)were assessed using pre-validated WISC-IQ score test, BOT-2 test, PA questionnaire, and immunoassay techniques respectively. RESULTS WISC-IQ and BOT-2 set scores of intellectual and motor skills performance showed a significant correlation with physical activity status and the regulation of oxidative stress-free radicals in school children with mild and moderate ID following 12 weeks of moderate exercise. The intellectual and motor skills performance of the participants correlated positively with the increase in TAC activity and physical fitness scores and negatively with MDA, 8-OHdG, NO, and Total-OS, respectively. Stepwise multiple regression analysis of the demographic, physical status and oxidative stress parameters explained around78.0 to 93.4 % of intellectual disability variation among schoolchildren. CONCLUSION Moderate aerobic training for12 weeks has a positive impact on improving intellectual ability of schoolchildren with ID via modulating redox status, improves physical fitness, and motor skills proficiency.

RESUMO OBJETIVO A baixa aptidão física e o baixo desempenho motor mostraram-se associados a níveis mais altos de estresse oxidativo em crianças e adolescentes com deficiência intelectual. Portanto, foi realizado um exercício aeróbico moderado por 12 semanas para avaliar os efeitos dos escores de atividade física nas funções motoras, estresse oxidativo e quocientes de inteligência (QI) em escolares com deficiência intelectual. MÉTODOS Um total de 65 crianças em idade escolar (12 a 18 anos) foi incluído aleatoriamente neste estudo. A incapacidade intelectual (DI), habilidades motoras, aptidão física (VO2máx), gasto energético total (ETE), MDA, 8-OHdG, TAC, NO e estresse oxidativo total (SG) foram avaliados pelo teste de pontuação Wisc-IQ pré-validado, teste BOT-2, questionário de PA e técnicas de imunoensaio, respectivamente. RESULTADOS Os escores do conjunto Wisc-IQ e BOT-2 do desempenho das habilidades intelectuais e motoras mostraram uma correlação significativa com o status da atividade física e a regulação dos radicais livres do estresse oxidativo em escolares com DI leve e moderada após 12 semanas de exercício moderado. O desempenho das habilidades intelectuais e motoras dos participantes correlacionou-se positivamente com o aumento dos escores de atividade TAC e aptidão física e negativamente com MDA, 8-OHdG, NO e Total-OS, respectivamente. Houve uma melhora significativa nas habilidades motoras, como áreas específicas de precisão motora fina, velocidade de corrida, agilidade, coordenação de membros superiores, força, coordenação bilateral e equilíbrio entre crianças em idade escolar após o programa de exercícios. A análise de regressão múltipla passo a passo dos parâmetros demográficos, do estado físico e do estresse oxidativo explicou em torno de 78,0 a 93,4% da variação da incapacidade intelectual entre os escolares. CONCLUSÃO O treinamento aeróbico moderado por 12 semanas tem um impacto positivo na melhoria da capacidade intelectual de escolares com DI por meio da modulação do status redox, melhora da aptidão física e proficiência em habilidades motoras.

Reduction of oxidative stress improves insulin signaling in cardiac tissue of obese mice / Redução do estresse oxidativo melhora a sinalização da insulina em tecido cardíaco de camundongos obesos

ABSTRACT Objective To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. Methods Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. Results Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. Conclusion Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.

RESUMO Objetivo Avaliar os efeitos do estresse oxidativo sobre a sinalização da insulina em tecido cardíaco de camundongos obesos. Métodos Utilizaram-se 30 camundongos Swiss subdivididos igualmente (n=10) em três grupos: Grupo Controle, Grupo Obeso e Grupo Obeso Tratado com N-acetilcisteína. Após estabelecidas a obesidade e a resistência à insulina, os camundongos obesos foram tratados diariamente, durante 15 dias, via gavagem oral, com N-acetilcisteína na dose de 50mg/kg. Resultados Observaram-se maiores níveis de glicose sanguínea, conteúdos de nitrito e carbonil, e menores níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada no Grupo Obeso quando comparado a seu respectivo controle. Por outro lado, o tratamento com N-acetilcisteína se mostrou eficiente em diminuir os níveis glicêmicos, os conteúdos de nitrito e carbonil, e aumentar significativamente os níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada, quando comparados ao Grupo Obeso. Conclusão Obesidade e/ou dieta hiperlipídica levam a estresse oxidativo e à resistência à insulina no tecido cardíaco de camundongos obesos, e o uso da N-acetilcisteína como estratégia metodológica e terapêutica sugeriu haver relação entre ambos.

Acute effect of passive cycle-ergometry and functional electrical stimulation on nitrosative stress and inflammatory cytokines in mechanically ventilated critically ill patients: a randomized controlled trial

Early mobilization is beneficial for critically ill patients because it reduces muscle weakness acquired in intensive care units. The objective of this study was to assess the effect of functional electrical stimulation (FES) and passive cycle ergometry (PCE) on the nitrous stress and inflammatory cytometry in critically ill patients. This was a controlled, randomized, open clinical trial carried out in a 16-bed intensive care unit. The patients were randomized into four groups: Control group (n=10), did not undergo any therapeutic intervention during the study; PCE group (n=9), lower-limb PCE for 30 cycles/min for 20 min; FES group (n=9), electrical stimulation of quadriceps muscle for 20 min; and FES with PCE group (n=7), patients underwent PCE and FES, with their order determined randomly. The serum levels of nitric oxide, tumor necrosis factor alpha, interferon gamma, and interleukins 6 and 10 were analyzed before and after the intervention. There were no differences in clinical or demographic characteristics between the groups. The results revealed reduced nitric oxide concentrations one hour after using PCE (P<0.001) and FES (P<0.05), thereby indicating that these therapies may reduce cellular nitrosative stress when applied separately. Tumor necrosis factor alpha levels were reduced after the PCE intervention (P=0.049). PCE and FES reduced nitric oxide levels, demonstrating beneficial effects on the reduction of nitrosative stress. PCE was the only treatment that reduced the tumor necrosis factor alpha concentration.

Effects of oxidative stress on liver, brain and spinal cord of rats using L-NAME and treated with hydroxyurea. A model of sickle cell complication

Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

Evaluation of nutritional risk factors in hematopoietic stem cell transplantation-eligible patients / Avaliação dos fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética

ABSTRACT Objective To evaluate the nutritional risk factors in patients eligible for hematopoietic stem cell transplantation. Methods A cross-sectional, descriptive study conducted with patients recruited from an hematology outpatient clinic. Study variables included demographic and clinical data, patient-generated global subjective assessment findings, anthropometric indicators, food intake and oxidative stress levels. The level of significance was set at 5% (p<0.05). Results The sample comprised 72 patients, mean age of 48.93 years (14.5%). Multiple myeloma was the most prevalent condition (51.4%) in this sample. Most patients (55.6%) were overweight according to body mass index and at risk of cardiovascular disease according to waist circumference, conicity index and percentage of body fat. Sarcopenia was associated with risk of cardiovascular disease, hip-to-waist ratio (p=0.021), muscle strength depletion (p<0.001), food intake (p=0.023), reduced functional capacity (p=0.048), self-reported well-nourished status; p=0.044) and inadequate vitamin B6 (p=0.022) and manganese (p=0.026) intake. Elevated oxidative stress, detected in 33.3% of patients in this sample, was not associated with sarcopenia. Conclusion Most patients in this sample were overweight and sarcopenic. Lean mass depletion was associated with risk of cardiovascular disease, reduced muscle strength, food intake changes, reduced functional capacity, self-reported well-nourished status and inadequate intake of vitamin B6 and manganese, but not with oxidative stress.

RESUMO Objetivo Avaliar os fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética. Métodos Estudo transversal, descritivo, realizado com pacientes de um ambulatório de hematologia. As variáveis estudadas foram demográficas, dados clínicos, avaliação subjetiva global produzida pelo próprio paciente, indicadores antropométricos, ingestão alimentar e estresse oxidativo. Os dados foram considerados estatisticamente significativos quando p<0,05. Resultados A amostra do estudo foi constituída por 72 pacientes, com média de idade de 48,93 (14,5%) anos e com mieloma múltiplo (51,4%) como a patologia mais prevalente. Conforme índice de massa corporal, 55,6% dos pacientes encontravam-se com excesso de peso. De acordo com a circunferência da cintura, índice de conicidade e percentual de gordura corporal, houve prevalência de risco para doença cardiovascular. A sarcopenia foi associada ao risco de doença cardiovascular pela relação cintura/quadril (p=0,021), depleção da força muscular (p<0,001), além da ingestão alimentar (p=0,023), da capacidade funcional reduzida (p=0,048) e do diagnóstico de "bem nutrido" (p=0,044), conforme a avaliação subjetiva global, e com consumo inadequado de vitamina B6 (p=0,022) e de manganês (p=0,026). Dentre os avaliados, 33,3% apresentaram estresse oxidativo elevado sem associação com sarcopenia. Conclusão Pacientes do pré-transplante se apresentam, em sua maioria, com excesso de peso, mas com sarcopenia, estando essa ausência de massa magra associada a risco de doença cardiovascular, depleção da força muscular, alteração da ingestão alimentar, redução da capacidade funcional, classificação de "bem nutrido", segundo a avaliação subjetiva global e consumo inadequado de vitamina B6 e manganês, não estando associada a estresse oxidativo.

Oxidative stress, telomere length, and frailty in an old age population

Abstract Background A global aging population requires focusing on the risk factors for unhealthy aging, preventive medicine, and chronic disease management. The identification of adverse health outcomes in older adults has been addressed by the characterization of frailty as a biological syndrome. In this field, oxidative stress and telomere length have been suggested as biomarkers of aging Objective The objective of the study was to study the association of oxidative stress, telomere length, and frailty in an old age population Methods We conducted a cross-sectional study based on 2015 data from 202 members of a cohort of older adults (n = 202; F/M gender ratio: 133/69; mean age: 69.89 ± 7.39 years). Reactive oxygen species were measured by dichlorofluorescein diacetate and lipid peroxidation by malondialdehyde. Telomere length was determined using quantitative polymerase chain reaction with SYBR Green Master Mix Results Statistical analysis showed an association between telomere length and frailty but no association between oxidative stress and telomere length or frailty Conclusions Telomere length could eventually be used as a marker to differentiate between healthy and unhealthy aging as expressed by frailty phenotype; oxidative stress seemed merely a biological process of aging.