Antioxidant Therapy in Inflammatory Bowel Disease: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials.

The objective of this study is to assess the effectiveness of treatment for inflammatory bowel diseases in modulating oxidative stress biomarkers and cytokine levels. A systematic review of clinical trials was conducted, searching electronic databases including PubMed, Science Direct, and Scopus. After excluding articles that did not meet the inclusion criteria, 19 studies were included in the systematic review and 8 in the meta-analysis (6 for antioxidant capacity, 6 for superoxide dismutase (SOD), and 5 for lipid peroxidation analyzed through malondialdehyde (MDA) levels). SOD was significantly modulated (RR = 0.3764, 95% CI [0.0262 to 0.7267], p = 0.035) but not antioxidant capacity (RR = 0.3424, 95% CI [0.0334 to 0.7183], p = 0.0742) or MDA (RR = -0.8534, 95% CI [-1.9333 to 0.2265], p = 0.1214). Nonetheless, studies investigating oxidative stress biomarkers and cytokines in the context of alternative therapies for IBD treatment are still scarce. This review highlights the potential of antioxidant supplementation in IBD management and underscores the need for further investigations into its effects on oxidative stress biomarkers and cytokines to improve therapeutic approaches for IBD patients.

Extraintestinal Manifestations in Induced Colitis: Controversial Effects of N-Acetylcysteine on Colon, Liver, and Kidney.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N-acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38th day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H2O2)) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF-α, and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF-α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease.

MUSCLE DEPLETED OBESITY IN INDIVIDUALS SCREENED FOR COLORECTAL CÂNCER.

BACKGROUND: Colorectal cancer (CRC) is the third most incident cancer in the world and the second leading cause of cancer death. Significant decreases in incidence and mortality can be achieved by reducing risk factors and adhering to healthy lifestyle recommendations, as well as screening for the disease. OBJECTIVE: To evaluate the clinical nutritional profile of individuals at medium risk screened for CRC residing in the city of Piranhas/Alagoas. METHODS: Cross-sectional study conducted from September to October 2020, with individuals at medium risk for CRC, of both sexes and aged between 50 and 70 years old. Participants were screened for CRC with fecal immunochemical testing (FIT) and colonoscopy. Personal, socioeconomic, clinical, lifestyle and nutritional assessment data were collected. The latter was performed using anthropometric data (weight, height, arm circumference and triceps skinfold thickness), body composition (bioimpedance) and physical examination. Descriptive analysis of data frequencies and dichotomization according to the presence or absence of overweight was performed, followed by comparison of means and medians and frequencies by chi-square or Fisher's exact test. RESULTS: In total, 82 people agreed to undergo the clinical nutritional assessment, most of them female (56.1%; n=46), adults (56.1%; n=46), with a mean age of 59.02 years (±6.30 SD). Pre-cancerous lesions were identified in 54.5% (n=42) of those screened, 52.4% (n=43) were smokers or former smokers, and 65.9% (n=54) did not practice scheduled physical activity. Nutritional assessment showed that 64.6% (n=53) were overweight according to body mass index. On the other hand, the muscle mass, % arm muscle circumference adequacy and body muscle mass (kg) markers showed that 32.9% (n=27) and 47.6% (n=39) of the subjects were muscle depleted, respectively. Above all, overweight participants had, in parallel, lower muscle mass (P<0.05), suggesting sarcopenic obesity in this population. CONCLUSION: Obesity is one of the main risk factors for CRC; when concomitant with sarcopenia, it favors worse health outcomes. In this context, evidence shows the need to assess muscle composition in people with obesity, especially through other methods of assessing body composition. Our results add to the evidence on the importance of the population being guided about screening and adherence to healthy lifestyle recommendations, especially strategies aimed at weight control and the practice of physical activity.

Obesidade com depleção muscular em indivíduos rastreados para o câncer colorretal / Muscle depleted obesity in individuals screened for colorectal câncer

ABSTRACT Background: Colorectal cancer (CRC) is the third most incident cancer in the world and the second leading cause of cancer death. Significant decreases in incidence and mortality can be achieved by reducing risk factors and adhering to healthy lifestyle recommendations, as well as screening for the disease. Objective: To evaluate the clinical nutritional profile of individuals at medium risk screened for CRC residing in the city of Piranhas/Alagoas. Methods: Cross-sectional study conducted from September to October 2020, with individuals at medium risk for CRC, of both sexes and aged between 50 and 70 years old. Participants were screened for CRC with fecal immunochemical testing (FIT) and colonoscopy. Personal, socioeconomic, clinical, lifestyle and nutritional assessment data were collected. The latter was performed using anthropometric data (weight, height, arm circumference and triceps skinfold thickness), body composition (bioimpedance) and physical examination. Descriptive analysis of data frequencies and dichotomization according to the presence or absence of overweight was performed, followed by comparison of means and medians and frequencies by chi-square or Fisher's exact test. Results: In total, 82 people agreed to undergo the clinical nutritional assessment, most of them female (56.1%; n=46), adults (56.1%; n=46), with a mean age of 59.02 years (±6.30 SD). Pre-cancerous lesions were identified in 54.5% (n=42) of those screened, 52.4% (n=43) were smokers or former smokers, and 65.9% (n=54) did not practice scheduled physical activity. Nutritional assessment showed that 64.6% (n=53) were overweight according to body mass index. On the other hand, the muscle mass, % arm muscle circumference adequacy and body muscle mass (kg) markers showed that 32.9% (n=27) and 47.6% (n=39) of the subjects were muscle depleted, respectively. Above all, overweight participants had, in parallel, lower muscle mass (P<0.05), suggesting sarcopenic obesity in this population. Conclusion: Obesity is one of the main risk factors for CRC; when concomitant with sarcopenia, it favors worse health outcomes. In this context, evidence shows the need to assess muscle composition in people with obesity, especially through other methods of assessing body composition. Our results add to the evidence on the importance of the population being guided about screening and adherence to healthy lifestyle recommendations, especially strategies aimed at weight control and the practice of physical activity.

RESUMO Contexto: O câncer colorretal (CCR) é o terceiro câncer mais incidente no mundo e a segunda principal causa de morte por câncer. Diminuições significativas da incidência e mortalidade podem ser alcançadas a partir da redução de fatores de risco e adesão às recomendações de estilo de vida saudável, bem como rastreamento da doença. Objetivo: Avaliar o perfil clínico nutricional de indivíduos em risco médio rastreados para o CCR residentes na cidade de Piranhas/Alagoas. Métodos: Estudo transversal, conduzido de setembro a outubro de 2020, com indivíduos de médio risco para o CCR, de ambos os sexos e idades entre 50 e 70 anos. Os participantes realizaram rastreamento para o CCR com teste imunoquímico fecal (FIT) e colonoscopia. Foram coletados dados pessoais, socioeconômicos, clínicos, de estilo de vida e avaliação nutricional. Esta última foi realizada através de dados antropométricos (peso, altura, circunferência do braço e prega cutânea tricipital), composição corporal (bioimpedância) e exame físico. Foi realizada análise descritiva das frequências dos dados e dicotomização segundo a presença ou não de excesso de peso, seguida da comparação de médias e medianas e das frequências por qui-quadrado ou teste exato de Fisher. Resultados: No total, 82 pessoas aceitaram realizar a avaliação clínica nutricional, a maioria do sexo feminino (56,1%; n=46), adultos (56,1%; n=46), com média de idade de 59,02 anos (±6,30 DP). Foram identificadas lesões pré-cancerígenas em 54,5% (n=42) dos rastreados, 52,4% (n=43) eram tabagista ou ex-tabagista e 65,9% (n=54) não praticavam atividade física programada. A avaliação nutricional demonstrou que 64,6% (n=53) estavam com excesso de peso pelo índice de massa corporal (IMC). Em contrapartida, os marcadores de massa muscular, % de adequação da circunferência muscular do braço (CMB) e massa muscular corporal (kg), mostraram que 32,9% (n=27) e 47,6% (n=39) dos indivíduos estavam com depleção muscular, respectivamente. Sobretudo os participantes com excesso de peso apresentavam, paralelamente, menor massa muscular (P<0,05), sugerindo obesidade sarcopênica nessa população. Conclusão: A obesidade é um dos principais fatores de risco para o CCR; quando concomitante a sarcopenia, favorece a piores desfechos para saúde. Nesse contexto, as evidências mostram a necessidade de avaliar a composição muscular em pessoas com obesidade, sobretudo, por outros métodos de avaliação da composição corporal. Nossos resultados se somam as evidências sobre a importância da população ser orientada sobre o rastreamento e adesão às recomendações de estilo de vida saudável, principalmente estratégias voltadas para o controle de peso e a prática de atividade física.

The impact on colostrum oxidative stress, cytokines, and immune cells composition after SARS-CoV-2 infection during pregnancy.

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19). Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum. Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H2O2, MPO) and for IL-1ß, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-ß, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum. Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H2O2, IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3-CD56brightCD16-CD27+IFN-γ+ and CD3-CD56dimCD16+CD27- were also increased. Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness.

Lack of Concordance among Nutritional Diagnostic Methods in Newly Diagnosed Colorectal Cancer Patients.

This study aimed to investigate the concordance of different nutritional assessment methods and the prevalence of inadequate nutritional status in newly diagnosed Colorectal cancer (CRC) patients. Cross sectional study was conducted in a public hospital in Alagoas, Brazil. Clinical, nutritional (patient-generated subjective global assessment [PG-SGA], body mass index [BMI], arm circumference [AC], triceps skinfold [TSF], arm muscle circumference [AMC]) and functional (handgrip strength [HGS]) data were collected from July 2017-January 2019. Of the 31 CRC patients with a mean age of 58.97 ± 14.96 years, 48.4% were elderly and 51.6% were female. TSF adequacy (80.8%) and PG-SGA (80.0%) revealed the highest prevalence of malnutrition. BMI identified the same prevalence of malnutrition and excess weight (30.0%). The concordance between PG-SGA and BMI (kappa = 0.086; p = 0.426) was slight, with fair HGS (kappa = 0.268; p = 0.124). PG-SGA and AC (kappa = 0.015; p = 0.99), TSF (kappa = 0.195; p = 0.558) and AMC adequacy (kappa = 0.142; p = 0.380) were poor. PG-SGA can diagnose malnutrition, even in those who are eutrophic/overweight, by other methods. Various methods do not show concordance with PG-SGA, confirming the need for both objective and subjective methods for better diagnosis of CRC patients.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Interleukin-6 and triceps skinfold are associated with severity/cancer stage in newly-diagnosed colorectal cancer patients / La interleucina-6 y el pliegue cutáneo del tríceps están relacionados con el estadio de gravedad del cáncer en los pacientes con cáncer colorrectal recién diagnosticados

Introduction: colorectal cancer (CRC) has an important impact on morbidity and mortality globally, and nitroxidative stress, inflammation, and nutritional status are linked with its progression. Aim: to analyze the association of inflammatory, anthropometric, functional, and oxidative markers with tumor stage in newly-diagnosed CRC patients at a public reference center in Maceió, Alagoas, Brazil. Methods: patient-generated subjective global assessment was applied, and weight, height, arm circumference, triceps skinfold (TSF), arm muscle circumference, and handgrip strength were obtained. A fasting blood sample was collected, centrifuged, and the serum was stored at -80 °C until the analysis. Malonaldehyde levels were quantified by HPLC (high-performance liquid chromatography) and cytokines, namely tumor necrosis factor-alpha, and interleukins IL-6, IL-8, and IL-17 were analyzed by ELISA. Patients were grouped according to cancer stage into group 1 (stage 0-III) and group 2 (stage IV). A binary logistic regression analysis was performed, adjusted for sex and age, to assess the relationships between the variables studied and cancer stage. Significance was considered when p < 0.05. Results: twenty-eight CRC patients were included, twenty (71.4 %) from group 1 and eight (28.6 %) from group 2. The binary logistic regression revealed that lower TSF adequacy (OR = 0.929; CI 95 % = 0.870-0.993; p = 0.029) and higher IL-6 levels (OR = 1.001; CI 95 % = 1.000-1.002; p = 0.012) increased the chance of patients having tumor stage IV. (AU)

Introducción: el cáncer colorrectal (CCR) tiene un impacto importante en la morbilidad y mortalidad a nivel mundial, y el estrés nitroxidativo, la inflamación y el estado nutricional están relacionados con su progresión. Objetivos: analizar la asociación de los marcadores inflamatorios, antropométricos, funcionales y oxidativos con el estadio tumoral de pacientes con CCR recién diagnosticados en un centro público de referencia de Maceió, Alagoas, Brasil. Métodos: se aplicó la valoración global subjetiva generada por el paciente y se obtuvieron el peso, la altura, la circunferencia del brazo, el pliegue cutáneo del tríceps (PCT), la circunferencia del músculo del brazo y la fuerza de prensión. Se tomó una muestra de sangre en ayunas, se centrifugó y el suero se almacenó a -80 °C hasta el momento del análisis. Los niveles de malonaldehído se cuantificaron por CLAR (cromatografía líquida de alta resolución) y las citocinas, representadas por el factor de necrosis tumoral alfa y las interleucinas IL-6, IL-8 e IL-17, se analizaron mediante ELISA. Los pacientes se agruparon según el estadio del cáncer en grupo 1 (estadio 0-III) y grupo 2 (estadio IV). Se realizó una regresión logística binaria, ajustada por sexo y edad, para evaluar las relaciones entre las variables estudiadas y el estadio del cáncer. Se consideró la significancia cuando p < 0,05. Resultados: se incluyeron veintiocho pacientes con CCR, de los cuales veinte (71,4 %) eran del grupo 1 y ocho (28,6 %) del grupo 2. La regresión logística binaria reveló que una menor adecuación de PCT (OR = 0,929; IC 95 % = 0,870-0,993; p = 0,029) y los niveles más altos de IL-6 (OR = 1,001; IC 95 % = 1,000-1,002; p = 0,012) aumentaban la probabilidad de que los pacientes tuvieran un tumor en estadio IV. (AU)

N-Acetylcysteine (NAC): Impacts on Human Health.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1ß) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC's relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

Biomarkers of placental redox imbalance in pregnancies with preeclampsia and consequent perinatal outcomes.

OBJECTIVE: To compare redox and inflammatory markers between normal and PE-derived placentas and to evaluate the relationship between placental redox imbalance markers and perinatal outcomes in pregnancies with PE. METHODS: This was a cross-sectional study conducted at the maternity hospital of a university hospital in Maceio-Alagoas, Brazil, in 2017, including women diagnosed with PE and healthy pregnant women and their conceptuses. After screening, standardized questionnaires containing socioeconomic, clinical, obstetric and anthropometric data were applied. After delivery, placental samples were collected for quantification of biomarkers of redox imbalance (catalase - CAT; malondialdehyde - MDA; hydrogen peroxide - H2O2; superoxide dismutase - SOD; reduced glutathione - GSH; oxidized glutathione - GSSG; and their ratio - GSH/GSSG) and inflammation (myeloperoxidase - MPO; interleukin (IL)-6; IL-8; IL-10; and tumor necrosis factor-alpha - TNF-α). All biomarkers were evaluated via linear regression with adjustments of variables with measures of weight, length, head circumference (HC), chest circumference (CC) and gestational age of newborns at birth, considering p < 0.05 as significant. RESULTS: A total of 100 pregnant women with PE and 50 healthy pregnant women were studied. Higher placental levels of catalase (p = 0.018), SOD (p = 0.031), the GSH/GSSG ratio (p = 0.019) and IL-6 (p = 0.010) and lower GSSG (p = 0.001) were observed in pregnant women with PE than in the control group. Positive associations between placental GSH levels and body weight, HC, CC and gestational age at birth (p < 0.05) were identified. CONCLUSION: PE-derived placentas had high concentrations of some antioxidants (enzymes and thiols), which might be a compensation mechanism against oxidative stress. Placental GSH levels were the only biomarker, among the studied ones, related positively with beneficial perinatal outcomes, suggesting that this endogenous antioxidant plays an important role in maintaining the health of the conceptus and women with PE.

3-Amino-1,2,4-Triazole Induces Quick and Strong Fat Loss in Mice with High Fat-Induced Metabolic Syndrome.

BACKGROUND: Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS. METHODS: Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg-1·24 h-1) for 12 weeks. RESULTS: The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels. CONCLUSIONS: In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status.

The Close Interplay of Nitro-Oxidative Stress, Advanced Glycation end Products and Inflammation in Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory Bowel Disease (IBD) exhibits no defined aetiology. However, factors such as genetic and nitro-oxidative stress are associated with chronic inflammation and IBD progression to Colorectal Cancer (CRC). The present review discusses the association of nitro-oxidative stress, inflammation and Advanced Glycation End products (AGE) and their corresponding receptor (RAGE) in IBD and examines the connection between these factors and nuclear factors, such as Nuclear Factor Kappa B (NF-κB), factorerythroid 2-related factor-2 (Nrf2), and p53 Mutant (p53M). METHODS: We searched the PubMed, ScienceDirect and Web of Science databases using a combination of the following terms: IBD, CRC, oxidative stress, inflammation, NF-κB, Nrf2, p53M, AGE and RAGE. RESULTS: Oxidative stress and inflammation activated two cellular pathways, the nuclear expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF-κB and p53M, which is associated with NF-κB activation, Deoxyribonucleic acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti-inflammatory genes, and is inhibited by chronic oxidative stress, NF-κB and p53M. AGE/RAGE are involved in inflammation progression because RAGE polymorphisms and increased RAGE levels are found in IBD patients. Alterations of these pathways in combination with oxidative damage are responsible for IBD symptoms and the progression to CRC. CONCLUSION: IBD is an inflammatory and nitro-oxidative stress-based bowel disease. Achieving a molecular understanding of the biochemical events and their complicated interactions will impact basic and applied research, animal models, and clinical trials.

Cross-Talk between Oxidative Stress and Inflammation in Preeclampsia.

The occurrence of hypertensive syndromes during pregnancy leads to high rates of maternal-fetal morbidity and mortality. Amongst them, preeclampsia (PE) is one of the most common. This review aims to describe the relationship between oxidative stress and inflammation in PE, aiming to reinforce its importance in the context of the disease and to discuss perspectives on clinical and nutritional treatment, in this line of research. Despite the still incomplete understanding of the pathophysiology of PE, it is well accepted that there are placental changes in pregnancy, associated with an imbalance between the production of reactive oxygen species and the antioxidant defence system, characterizing the placental oxidative stress that leads to an increase in the production of proinflammatory cytokines. Hence, a generalized inflammatory process occurs, besides the presence of progressive vascular endothelial damage, leading to the dysfunction of the placenta. There is no consensus in the literature on the best strategies for prevention and treatment of the disease, especially for the control of oxidative stress and inflammation. In view of the above, it is evident the important connection between oxidative stress and inflammatory process in the pathogenesis of PE, being that this disease is capable of causing serious implications on both maternal and fetal health. Reports on the use of anti-inflammatory and antioxidant compounds are analysed and still considered controversial. As such, the field is open for new basic and clinical research, aiming the development of innovative therapeutic approaches to prevent and to treat PE.

PRE-OPERATIVE FASTING: WHY ABBREVIATE?

INTRODUCTION: Considering the practice of preoperative fasting based on observations on the gastric emptying delay after induction and the time of this fast is closely linked to organic response to trauma, arise the question about preoperative fasting period necessary to minimize such response and support the professional with clinical and scientific evidence. AIM: To review the aspects related to the abbreviation of preoperative fasting from the metabolic point of view, physiology of gastric emptying, its clinical benefits and the currently recommendations. METHOD: Literature review was based on articles and guidelines published in English and Portuguese, without restriction of time until January 2017, in PubMed, SciELO and Cochrane with the descriptors: surgery, preoperative fasting, carbohydrate. From the universe consulted, 31 articles were selected. RESULTS: The literature suggests that the abbreviation of fasting with beverage added carbohydrates until 2 h before surgery, can bring benefits on glycemic and functional parameters, reduces hospitalization, and does not present aspiration risk of healthy patients undergoing elective surgery. Another nutrient that has been added to the carbohydrate solution and has shown promising results is glutamine. CONCLUSION: The abbreviation of preoperative fasting with enriched beverage with carbohydrates or carbohydrate and glutamine seems to be effective in the care of the surgical patient, optimizing the recovery from of postoperative period.

Pre-operative fasting: why abbreviate? / Jejum pré-operatório: por que abreviar?

ABSTRACT Introduction : Considering the practice of preoperative fasting based on observations on the gastric emptying delay after induction and the time of this fast is closely linked to organic response to trauma, arise the question about preoperative fasting period necessary to minimize such response and support the professional with clinical and scientific evidence. Aim : To review the aspects related to the abbreviation of preoperative fasting from the metabolic point of view, physiology of gastric emptying, its clinical benefits and the currently recommendations. Method : Literature review was based on articles and guidelines published in English and Portuguese, without restriction of time until January 2017, in PubMed, SciELO and Cochrane with the descriptors: surgery, preoperative fasting, carbohydrate. From the universe consulted, 31 articles were selected. Results : The literature suggests that the abbreviation of fasting with beverage added carbohydrates until 2 h before surgery, can bring benefits on glycemic and functional parameters, reduces hospitalization, and does not present aspiration risk of healthy patients undergoing elective surgery. Another nutrient that has been added to the carbohydrate solution and has shown promising results is glutamine. Conclusion : The abbreviation of preoperative fasting with enriched beverage with carbohydrates or carbohydrate and glutamine seems to be effective in the care of the surgical patient, optimizing the recovery from of postoperative period.

RESUMO Introdução : Considerando que a prática do jejum pré-operatório é baseada nas observações do retardo do esvaziamento gástrico após a indução anestésica e que o tempo deste jejum está intimamente ligado à resposta orgânica ao trauma, surge o questionamento acerca do período de jejum necessário para minimizar tal resposta e respaldar a atuação profissional em evidências clinicocientíficas. Objetivo : Revisar a abreviação do jejum pré-operatório, sob o ponto de vista metabólico, da fisiologia do esvaziamento gástrico, seus benefícios clínicos e recomendações atualmente vigentes. Método : A revisão foi baseada em artigos e guidelines publicados em inglês e português, sem restrição de tempo até janeiro de 2017, no PubMed, SciELO e Cochrane com os descritores: cirurgia, jejum pré-operatório, carboidrato. Do universo consultado 31 artigos foram selecionados. Resultados : A literatura aponta que a abreviação do jejum com bebida enriquecida com carboidratos até 2 h antes do procedimento cirúrgico pode trazer benefícios sobre parâmetros glicêmicos, funcionais, redução da hospitalização, além de não oferecer risco de broncoaspiração em indivíduos saudáveis submetidos à operações eletivas. Outro nutriente frequentemente adicionado a esta solução de carboidratos, com resultados promissores, é a glutamina. Conclusão : A abreviação do jejum pré-operatório com bebida enriquecida com carboidratos ou carboidratos e glutamina parece mostrar-se eficaz no cuidado ao paciente cirúrgico otimizando a recuperação do período pós-operatório.

Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats.

Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day-1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage.

Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine.

Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized by increased OS or decreased glutathione (GSH) level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59) of the cases evaluated (n = 69, 100%). Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription.

Antioxidant therapy for treatment of inflammatory bowel disease: Does it work?

Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies.

Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1ß.

This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1ß. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1ß, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.