Gamma-oryzanol reduces renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to high sugar-fat diet / Gama-orizanol reduz a inflamação e o estresse oxidativo nos rins pela modulação do eixo RAGE/AGEs em animais submetidos a uma dieta rica em gordura e açúcar

Abstract Introduction: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities. Aim: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet. Methods: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks. Results: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz. Conclusion: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.

Resumo Introdução: O receptor para AGEs (RAGE) é um membro multiligante da superfamília das imunoglobulinas dos receptores de superfície celular expresso em muitos órgãos, entre eles, os rins. Quando ativado, o RAGE leva a uma sequência de sinalização que resulta em inflamação e estresse oxidativo, ambos envolvidos na patogênese de doenças renais. O gama-orizanol (γOz) compreende uma mistura de ésteres de ácido ferúlico (AF) e fitoesteróis (esteróis e álcoois triterpenos) encontrados principalmente no arroz, com atividades antioxidantes e anti-inflamatórias. Objetivo: Avaliar o efeito do γOz para reduzir a inflamação renal e o estresse oxidativo pela modulação do eixo RAGE/AGEs em animais submetidos a uma dieta rica em gordura e açúcar. Métodos: Ratos Wistar machos (±187g) foram divididos aleatoriamente em dois grupos experimentais: controle (n = 7 animais) e dieta rica em gordura e açúcar (HSF, do inglês high sugar-fat diet, n = 14 animais) por 20 semanas. Após este período, quando foi detectada a presença de fatores de risco de doença renal no grupo HSF (resistência à insulina, dislipidemia, aumento da pressão arterial sistólica e obesidade), os animais HSF foram divididos para iniciar o tratamento com γOz ou continuar recebendo apenas HSF por mais 10 semanas. Resultados: Não foi observado nenhum efeito do γOz na obesidade e nos parâmetros metabólicos. No entanto, a inflamação e o estresse oxidativo renais diminuíram assim que os níveis de RAGE foram reduzidos em HSF + γOz. Conclusão: É possível concluir que o gama- orizanol foi eficaz em reduzir a inflamação e o estresse oxidativo no rim pela modulação do eixo RAGE/AGEs.

Gamma-oryzanol reduces renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to high sugar-fat diet.

INTRODUCTION: The receptor for AGEs (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface receptors expressed in many organs, among them, the kidneys. When activated, RAGE leads to a sequence of signaling that results in inflammation and oxidative stress, both involved in kidney disease pathogenesis. Gamma-oryzanol (γOz) comprises a mixture of ferulic acid (FA) esters and phytosterols (sterols and triterpene alcohols) mainly found in rice, with antioxidant and anti-inflammatory activities. AIM: To evaluate the effect of γOz to reduce renal inflammation and oxidative stress by modulating AGEs/RAGE axis in animals submitted to a high sugar-fat diet. METHODS: Male Wistar rats (±187g) were randomly divided into two experimental groups: control (n = 7 animals) and high sugar-fat diet (HSF, n = 14 animals) for 20 weeks. After this period, when the presence of renal disease risk factors was detected in the HSF group (insulin resistance, dyslipidemia, increased systolic blood pressure and obesity), the HSF animals were divided to begin the treatment with γOz or continue receiving only HSF for 10 more weeks. RESULTS: No effect of γOz on obesity and metabolic parameters was observed. However, kidney inflammation and oxidative stress decreased as soon as RAGE levels were reduced in HSF + γOz. CONCLUSION: It is possible to conclude that the gamma- oryzanol was effective in reducing inflammation and oxidative stress in the kidney by modulating the AGEs/RAGE axis.

Rice bran modulates renal disease risk factors in animals submitted to high sugar-fat diet / Farelo de arroz modula os fatores de risco de doença renal em animais submetidos a uma dieta rica em gordura e açúcar

Abstract Introduction: Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. Methods: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. Results: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)], insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)], dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)], inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. Conclusion: In conclusion, rice bran prevented renal disease by modulating risk factors.

Resumo Introdução: Obesidade, diabetes e hipertensão arterial são fatores de risco comuns para doenças renais crônicas (DRC). A DRC surge devido a muitos insultos patológicos, incluindo inflamação e estresse oxidativo, que afetam a função renal e destroem os néfrons. O farelo de arroz (FA) é rico em vitaminas e minerais, e contém uma quantidade significativa de antioxidantes. O objetivo deste estudo foi avaliar o efeito preventivo do FA nos fatores de risco de doenças renais. Métodos: Ratos Wistar machos (±325 g) foram divididos em dois grupos experimentais para receber uma dieta rica em gordura e açúcar (DRGA, n = 8) ou uma dieta rica em gordura e açúcar com farelo de arroz (DRGA + FA, n = 8) por 20 semanas. Ao final, foram analisados a função renal, composição corporal, parâmetros metabólicos, marcadores renais inflamatórios e de estresse oxidativo. Resultados: FA preveniu a obesidade [IA (DRGA= 9,92 ± 1,19 vs. DRGA + FA= 6,62 ± 0. 78)], resistência à insulina [HOMA (DRGA= 83 ± 8 vs DRGA + FA= 42 ± 11)], dislipidemia [TG (DRGA= 167 ± 41 vs. DRGA + FA=92 ± 40)], inflamação [FNT-α (DRGA= 80 ± 12 vs. DRGA + FA=57 ± 14), IL-6 (903 ± 274 vs. DRGA + FA= 535 ± 277)], estresse oxidativo [carbonilação de proteína (DRGA= 3. 38 ± 0,18 vs. DRGA + FA=2,68 ± 0,29), RAGE (DRGA=702 ± 36 vs. DRGA + FA=570 ± 190)], e doença renal [relação proteína/creatinina (DRGA=1,10 ± 0,38 vs. DRGA + FA=0,49 ± 0,16)]. Conclusão: Em conclusão, o farelo de arroz preveniu doenças renais através da modulação dos fatores de risco.

Differentially expressed proteins obtained by label-free quantitative proteomic analysis reveal affected biological processes and functions in Western diet-induced steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a pathological manifestation with a progressive incidence in response to the epidemic of hepatic steatosis caused primarily by excessive energy intake. The present study unravels affected biological processes and functions by the presence of NASH in rats using a label-free quantitative proteomic strategy. NASH was induced by a Western high-sugar and high-fat diet for 20 weeks. The liver tissue was collected for histology and for a mass spectrometry-based proteomic protocol. The NASH group showed severe lipidosis, hepatocyte ballooning, and the presence of collagen deposition. Among upregulated proteins in NASH perilipin-2 (Plin-2; F6QBA3; difference [diff]: 2.29), ferritin heavy (Fth1; Q66HI5; diff: 2.19) and light (Ftl1; P02793; diff: 1.75) chains, macrophage migration inhibitory factor 1 (Mif; P30904; diff: 1.69), and fibronectin (Fn1; F1LST1; diff: 0.35) were observed, whereas among downregulated proteins, plectin (Q6S399; diff: -3.34), some Cyp2 family proteins of the cytochrome P450 complex, glutathione S-transferases, flavin-containing monooxygenase 1 (Fmo1; P36365; diff: -2.08), acetyl-CoA acetyltransferase 2 (Acat2; Q5XI22; diff: -2.25), acyl-CoA oxidase 2 (Acox2; F1LNW3; diff: -1.59), and acyl-CoA oxidase 3 (Acox3; F1M9A7; diff: -2.41) were observed. Also, biological processes and functions such as LPS/IL-1 inhibition of RXR, fatty acid metabolism, Nrf2-mediated oxidative stress response, xenobiotic metabolism, and PXR/RXR and CAR/RXR activations were predicted to be affected. In conclusion, the liver of rats with NASH induced by Western diet shows a decreased capacity of metabolizing lipids, fatty acids, and xenobiotic compounds that predispose fibrosis development.

Rice bran modulates renal disease risk factors in animals submitted to high sugar-fat diet.

INTRODUCTION: Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains significant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. METHODS: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. RESULTS: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)], insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)], dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)], inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. CONCLUSION: In conclusion, rice bran prevented renal disease by modulating risk factors.

Gamma-oryzanol as a potential modulator of oxidative stress and inflammation via PPAR-y in adipose tissue: a hypothetical therapeutic for cytokine storm in COVID-19?

The literature has reported a higher prevalence of negative clinical outcomes due to Coronavirus disease 19 (COVID-19) in obese individuals. This can be explained by the cytokine storm, result from the cytokine production from both obesity and viral infection. Gamma-oryzanol (γOz) is a compound with anti-inflammatory and antioxidant activities. However, little is known about the γOz action as a possible agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of this study was to test the hypothesis that γOz attenuates the cytokine storm by stimulating PPAR-γ in the adipose tissue. METHODS: Male Wistar rats were randomly divided into three experimental groups and fed ad libitum for 30 weeks with control diet (C, n = 6), high sugar-fat diet (HSF, n = 6) or high sugar-fat diet + Î³Oz (HSF + Î³Oz, n = 6). HSF groups also received water + sucrose (25%). The γOz dose was 0.5% in the chow. Evaluation in animals included caloric intake, body weight, adiposity index, plasma triglycerides, and HOMA-IR. In adipose tissue was evaluated: PPAR-γ gene and protein expression, inflammatory and oxidative stress parameters, and histological analysis. RESULTS: Adipose tissue dysfunction was observed in HSF group, which presented remarkable PPAR-γ underexpression and increased levels of cytokines, other inflammatory markers and oxidative stress. The γOz treatment prevented adipose tissue dysfunction and promoted PPAR-γ overexpression. CONCLUSION: Natural compounds as γOz can be considered a coadjutant therapy to prevent the cytokine storm in COVID-19 patients with obesity conditions.

Protective Effect of Tomato-Oleoresin Supplementation on Oxidative Injury Recoveries Cardiac Function by Improving ß-Adrenergic Response in a Diet-Obesity Induced Model.

The system redox imbalance is one of the pathways related to obesity-related cardiac dysfunction. Lycopene is considered one of the best antioxidants. The aim of this study was to test if the tomato-oleoresin would be able to recovery cardiac function by improving ß-adrenergic response due its antioxidant effect. A total of 40 animals were randomly divided into two experimental groups to receive either the control diet (Control, n = 20) or a high sugar-fat diet (HSF, n = 20) for 20 weeks. Once cardiac dysfunction was detected by echocardiogram in the HSF group, animals were re- divided to begin the treatment with Tomato-oleoresin or vehicle, performing four groups: Control (n = 6); (Control + Ly, n = 6); HSF (n = 6) and (HSF + Ly, n = 6). Tomato oleoresin (10 mg lycopene/kg body weight (BW) per day) was given orally every morning for a 10-week period. The analysis included nutritional and plasma biochemical parameters, systolic blood pressure, oxidative parameters in plasma, heart, and cardiac analyses in vivo and in vitro. A comparison among the groups was performed by two-way analysis of variance (ANOVA). Results: The HSF diet was able to induce obesity, insulin-resistance, cardiac dysfunction, and oxidative damage. However, the tomato-oleoresin supplementation improved insulin-resistance, cardiac remodeling, and dysfunction by improving the ß-adrenergic response. It is possible to conclude that tomato-oleoresin is able to reduce the oxidative damage by improving the system's ß-adrenergic response, thus recovering cardiac function.

Basic Concepts on the Role of Nuclear Factor Erythroid-Derived 2-Like 2 (Nrf2) in Age-Related Diseases.

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is one of the most important oxidative stress regulator in the human body. Once Nrf2 regulates the expression of a large number of cytoprotective genes, it plays a crucial role in the prevention of several diseases, including age-related disorders. However, the involvement of Nrf2 on these conditions is complex and needs to be clarified. Here, a brief compilation of the Nrf2 enrollment in the pathophysiology of the most common age-related diseases and bring insights for future research on the Nrf2 pathway is described. This review shows a controversial response of this transcriptional factor on the presented diseases. This reinforces the necessity of more studies to investigate modulation strategies for Nrf2, making it a possible therapeutic target in the treatment of age-related disorders.

Association between Cardiac Remodeling and Metabolic Alteration in an Experimental Model of Obesity Induced by Western Diet.

The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as dyslipidemia, hypertension, and cardiovascular disease. The aim of this study was to evaluate the association between dyslipidemia and cardiac dysfunction induced by western diet consumption. Wistar rats were randomly divided into two experimental groups and fed ad libitum for 20 weeks with a control diet (Control, n = 12) or a high-sugar and high-fat diet (HSF, n = 12). The HSF group also received water + sucrose (25%). Evaluations included feed and caloric intake; body weight; plasma glucose; insulin; uric acid; HOMA-IR; lipid profile: [total cholesterol (T-chol), high-density lipoprotein (HDL), non-HDL Chol, triglycerides (TG)]; systolic blood pressure, and Doppler echocardiographic. Compared to the control group, animals that consumed the HSF diet presented higher weight gain, caloric intake, feed efficiency, insulin, HOMA-IR, and glucose levels, and lipid profile impairment (higher TG, T-chol, non-HDL chol and lower HDL). HSF diet was also associated with atrial-ventricular structural impairment and systolic-diastolic dysfunction. Positive correlation was also found among the following parameters: insulin versus estimated LV mass (r = 0.90, p = 0.001); non-HDL versus deceleration time (r = 0.46, p = 0.02); TG versus deceleration time (r = 0.50, p = 0.01). In summary, our results suggest cardiac remodeling lead by western diet is associated with metabolic parameters.

Factors that influence the redox state in children: An exploratory study.

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.

Gamma Oryzanol Treats Obesity-Induced Kidney Injuries by Modulating the Adiponectin Receptor 2/PPAR-α Axis.

The kidney is an important organ in the maintenance of body homeostasis. Dietary compounds, reactive metabolites, obesity, and metabolic syndrome (MetS) can affect renal filtration and whole body homeostasis, increasing the risk of chronic kidney disease (CKD) development. Gamma oryzanol (γOz) is a compound with antioxidant and anti-inflammatory activity that has shown a positive action in the treatment of obesity and metabolic diseases. Aim. To evaluate the effect of γOz to recover renal function in obese animals by high sugar-fat diet by modulation of adiponectin receptor 2/PPAR-α axis Methods. Male Wistar rats were initially randomly divided into 2 experimental groups: control and high sugar-fat diet (HSF) for 20 weeks. When proteinuria was detected, HSF animals were allocated to receive γOz or maintain HSF for more than 10 weeks. The following were analyzed: nutritional and biochemical parameters, systolic blood pressure, and renal function. In the kidney, the following were evaluated: inflammation, oxidative stress, and protein expression by Western blot. Results. After 10 weeks of γOz treatment, γOz was effective to improve inflammation, increase antioxidant enzyme activities, increase the protein expression of adiponectin receptor 2 and PPAR-α, and recover renal function. Conclusion. These results permit us to confirm that γOz is able to modulate PPAR-α expression, inflammation, and oxidative stress pathways improving obesity-induced renal disease.

Factors that influence the redox state in children: An exploratory study

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.

Metabolic syndrome and inflammation in adipose tissue occur at different times in animals submitted to a high-sugar/fat diet.

Obesity is associated with low-grade inflammation, triggered in adipose tissue, which may occur due to an excess of SFA from the diet that can be recognised by Toll-like receptor-4. This condition is involved in the development of components of the metabolic syndrome associated with obesity, especially insulin resistance. The aim of the study was to evaluate the manifestation of the metabolic syndrome and adipose tissue inflammation as a function of the period of time in which rats were submitted to a high-sugar/fat diet (HSF). Male Wistar rats were divided into six groups to receive the control diet (C) or the HSF for 6, 12 or 24 weeks. HSF increased the adiposity index in all HSF groups compared with the C group. HSF was associated with higher plasma TAG, glucose, insulin and leptin levels. Homeostasis model assessment increased in HSF compared with C rats at 24 weeks. Both TNF-α and IL-6 were elevated in the epididymal adipose tissue of HSF rats at 24 weeks compared with HSF at 6 weeks and C at 24 weeks. Only the HSF group at 24 weeks showed increased expression of both Toll-like receptor-4 and NF-κB. More inflammatory cells were found in the HSF group at 24 weeks. We can conclude that the metabolic syndrome occurs independently of the inflammatory response in adipose tissue and that inflammation is associated with hypertrophy of adipocytes, which varies according to duration of exposure to the HSF.

Yacon (Smallanthus sonchifolius) Leaf Extract Attenuates Hyperglycemia and Skeletal Muscle Oxidative Stress and Inflammation in Diabetic Rats.

The effects of hydroethanolic extract of Yacon leaves (HEYL) on antioxidant, glycemic, and inflammatory biomarkers were tested in diabetic rats. Outcome parameters included glucose, insulin, interleukin-6 (IL-6), and hydrophilic antioxidant capacity (HAC) in serum and IL-6, HAC, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in soleus. The rats (10/group) were divided as follows: C, controls; C + Y, HEYL treated; DM, diabetic controls; and DM + Y, diabetic rats treated with HEYL. Diabetes mellitus was induced by administration of streptozotocin. C + Y and DM + Y groups received 100 mg/kg HEYL daily via gavage for 30 d. Hyperglycemia was improved in the DM + Y versus DM group. Insulin was reduced in DM versus C group. DM rats had higher IL-6 and MDA and lower HAC in the soleus muscle. HEYL treatment decreased IL-6 and MDA and increased HAC in DM rats. DM + Y rats had the highest CAT activity versus the other groups; GPx was higher in C + Y and DM + Y versus their respective controls. The apparent benefit of HEYL may be mediated via improving glucoregulation and ameliorating oxidative stress and inflammation, particularly in diabetic rats.

The role of oxidative stress on the pathophysiology of metabolic syndrome.

Metabolic syndrome (MetS) has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

The role of oxidative stress on the pathophysiology of metabolic syndrome / O papel do estresse oxidativo na fisiopatologia da síndrome metabólica

Summary Metabolic syndrome (MetS) has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

Resumo A síndrome metabólica apresenta elevada prevalência na população mundial. De acordo com os componentes que a classificam, nota-se que está intimamente relacionada com a obesidade. Essas duas condições se iniciam com o aumento do tecido adiposo abdominal, o qual é metabolicamente mais ativo, contendo uma quantidade maior de macrófagos residentes em comparação com outros depósitos de gordura. Essa situação favorece a inflamação e o estresse oxidativo, ambos precursores de diversas complicações, mas principalmente as envolvidas na síndrome metabólica, como resistência à insulina, hipertensão arterial e hiperlipidemia. Uma maneira de bloquear os efeitos do estresse oxidativo seria pelo sistema de defesa antioxidante, o qual anula os radicais livres em excesso. É sabido que indivíduos portadores de síndrome metabólica e obesos apresentam um alto consumo de gorduras, açúcares oriundos de alimentos industrializados com alto teor de sódio e uma baixa ingestão de frutas e verduras, apresentando uma condição de estresse oxidativo contínuo. A manutenção de hábitos alimentares saudáveis, com a inclusão de alimentos ricos em antioxidantes, poderia prevenir ou retardar o surgimento da SM.

Renal inflammatory and oxidative and metabolic changes after 6 weeks of cafeteria diet in rats.

INTRODUCTION: Obesity is a disease in which inflammation is directly involved and can lead to impaired renal function. OBJECTIVE: To evaluate the influence of short term exposure to cafeteria diet on kidney tissue inflammation and advanced glycation end products (AGEs) in the rat plasma. METHODS: Male Wistar rats (10 weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8 animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6 weeks. RESULTS: adiposity index at six weeks was higher in CAF-D group compared to C. The same behavior was observed for plasma levels of glucose, triglycerides, leptin, insulin and AGEs. The gene expression of IL-6 and TNF-α in renal tissue was higher in CAF-D group and no significant difference in adipose tissue. There was no increase of these cytokines in plasma and kidney or histologically. There was a significant decrease of adiponectin in the CAF-D group. CONCLUSION: The short exposure CAF-D reflects changes in metabolism, increased plasma levels of AGEs, which may reflect the increased expression of inflammatory cytokines in the kidney.

Inflamação renal, alterações metabólicas e oxidativas após 6 semanas de dieta de cafeteria em ratos / Renal inflammatory and oxidative and metabolic changes after 6 weeks of cafeteria diet in rats

Resumo Introdução: A obesidade é uma doença em que a inflamação está inteiramente envolvida e pode causar insuficiência renal. Objetivo: Avaliar a influência da exposição a curto prazo de uma dieta de cafeteria sobre a inflamação no tecido renal e a formação de produtos de glicação avançada (AGEs) no plasma de rato. Métodos: Ratos Wistar machos (10 semanas de idade, pesando 350 g) foram designados para receber dieta de ração comercial (C; n = 8 animais/grupo, 5% de energia a partir de gordura) ou dieta de cafeteria (CAF-D, n = 8 animais/grupo: 29% de energia de gordura) e de sacarose em água (300 g/L) de beber durante 6 semanas. Resultados: Índice de adiposidade em seis semanas foi maior no grupo CAF-D em comparação com C. O mesmo comportamento foi observado para os níveis plasmáticos de glicose, triglicerídeos, leptina, insulina e AGEs. A expressão do gene de IL-6 e TNF-α em tecido renal foi maior no grupo D-CAF e nenhuma diferença significativa no tecido adiposo. Não houve aumento destas citocinas no plasma ou rim. Houve uma diminuição significativa de adiponectina no grupo CAF-D. Conclusão: A exposição a curto prazo da CAF-D reflete alterações no metabolismo, aumento dos níveis plasmáticos de AGEs, o que pode refletir o aumento expressão de citocinas inflamatórias no rim.

Abstract Introduction: Obesity is a disease in which inflammation is directly involved and can lead to impaired renal function. Objective: To evaluate the influence of short term exposure to cafeteria diet on kidney tissue inflammation and advanced glycation end products (AGEs) in the rat plasma. Methods: Male Wistar rats (10 weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8 animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6 weeks. Results: adiposity index at six weeks was higher in CAF-D group compared to C. The same behavior was observed for plasma levels of glucose, triglycerides, leptin, insulin and AGEs. The gene expression of IL-6 and TNF-α in renal tissue was higher in CAF-D group and no significant difference in adipose tissue. There was no increase of these cytokines in plasma and kidney or histologically. There was a significant decrease of adiponectin in the CAF-D group. Conclusion: The short exposure CAF-D reflects changes in metabolism, increased plasma levels of AGEs, which may reflect the increased expression of inflammatory cytokines in the kidney.

Fructose: Toxic effect on cardiorenal risk factors and redox state.

AIM: To investigate the effects of fructose consumption on the antioxidant capacity in heart and kidney, cardiovascular disease risk factors, and evaluation of these variables after its removal. METHODS: Male Wistar rats (n = 36) were divided into control group (n = 12): standard chow + water or F group: standard chow + fructose in drinking water (30%) for 15 weeks. After, F group was divided to continue receiving standard chow + fructose in drinking water (30%) (n = 12) or standard chow + water (Ex group, n = 12) for 9 weeks. Water, chow and caloric diaries intake, final body weight, adiposity index, plasma glucose and triacylglycerol, systolic blood pressure, and cardiac and renal hydrophilic antioxidant capacity were analyzed. RESULTS: Control and Ex groups consumed less chow and water compared to F group. Caloric intake was higher in control group. There was no difference in final body weight and adiposity index. Systolic blood pressure and cardiac and renal hydrophilic antioxidant capacity were worst in F group. CONCLUSION: Prolonged exposure to fructose induces oxidative stress, systolic blood pressure, and increase in triacylglycerol. When stopped fructose consumption, Ex group presented improvement in these variables, suggesting the toxicity effect of fructose when consumed in high amounts and prolonged exposure.

Balanced anesthesia with sevoflurane does not alter redox status in patients undergoing surgical procedures.

Despite the effectiveness and safety of anesthetics, some unanswered questions remain concerning their toxicity and effects on cellular redox balance. To test for possible toxic effects of balanced anesthesia maintained with the volatile anesthetic sevoflurane, we evaluated oxidative stress during and after general anesthesia in 15 adult patients without comorbidities who underwent elective minor surgical procedures. Venous blood samples were collected at baseline, before anesthesia (t0); after anesthesia induction and immediately before surgery (t1); 2h after the beginning of anesthesia (t2); and on the day following surgery (t3). Antioxidant defense was determined by fluorometry. Oxidative stress markers included oxidative DNA damage, evaluated by the alkaline comet assay, and plasma malondialdehyde (MDA), assessed by high performance liquid chromatography (HPLC). No increase in oxidized DNA damage or antioxidant defense was observed. Plasma MDA increased only at t3 compared with t2. Balanced sevoflurane-maintained anesthesia appears neither to damage DNA nor to alter redox status.