Rice (Oryza sativa L.) bran preserves cardiac function by modulating pro-inflammatory cytokines and redox state in the myocardium from obese rats.

PURPOSE: This study aimed to evaluate the effect of rice bran (RB) supplementation to a high-sugar fat (HSF) diet on cardiac dysfunction in an experimental obesity model. METHODS: Male Wistar rats were distributed into three groups: control, high-sugar fat, and high-sugar fat supplemented with 11% RB for 20 weeks. RESULTS: HSF diet promoted obesity and metabolic complications. Obese rats showed cardiac structural and functional impairment associated with high levels of interleukin-6, tumoral necrosis factor alpha, and malondialdehyde, and decreased activity of superoxide dismutase and catalase in the myocardium. RB supplementation was able to mitigate obesity and its metabolic alterations in HSF diet-fed animals. Moreover, the RB also prevented structural and functional damage, inflammation, and redox imbalance in the heart of these animals. CONCLUSION: This study suggests that RB supplementation prevents cardiac dysfunction in rats fed on HSF by modulating systemic metabolic complications and inflammation and oxidative stress in the myocardium, representing potential alternative therapy.

Tomato-Oleoresin Anti-Inflammatory Effect Recovers Obesity-Induced Cardiac Dysfunction by Modulating Myocardial Calcium Handling.

BACKGROUND/AIMS: Considering the importance of inflammation on obesity-related disorders pathogenesis, including cardiac dysfunction, the interest in natural anti-inflammatory therapeutic strategies has emerged. The lycopene is a carotenoid presents in tomato and red fruits that displays anti-inflammatory properties. In this sense, we will evaluate the anti-inflamma-tory effect of tomato-oleoresin supplementation on obesity- related cardiac dysfunction by modulating myocardial calcium kinetic. METHODS: Male Wistar rats were initially randomized into 2 experimental groups: (Control, n= 20) or high sugar- fat diet (HSF, n=20) for 20 weeks. At week 20th, once detected the cardiac dysfunction (cardiac remodeling, systolic and diastolic dysfunction) by echocardiography in HSF group, animals were randomly divided to begin the treatment with tomato-oleoresin, performing 4 groups: Control (n= 10); Control + tomato tomato-oleoresin supplementation (Control + Ly, n= 10); HSF (n= 10) or HSF + tomato tomato-oleoresin supplementation (HSF + Ly, n= 10). Tomato oleoresin was mixed with maize oil equivalent to 10mg lycopene/kg body weight (BW) per day and given orally, by gavage, every morning for a 10-week period. It was analyzed cardiac inflammatory parameters by the enzyme-linked immunosorbent assay (ELISA) and in vivo (echocardiography) and in vitro (studying isolated papillary muscles from the left ventricle) cardiac function. The groups were compared by Two-Way analysis of variance (ANOVA). RESULTS: The HSF diet induced cardiac dysfunction (FS(%) C: 60.4±1.3; C+Ly: 60.9±1.3; HSF: 51.7±1.3; HSF+Ly: 59.4±1.4) and inflammation (TNF-α: C:1.88±0.41; C+Ly: 1.93±1.01; HSF: 4.58±1.99; HSF+Ly: 2.03±0.55; IL-6: C:0.58±0.16; C+Ly: 0.40±0.16; HSF: 2.00±0.45; HSF+Ly: 0.53±0.26; MCP-1: C:0.31±0.08; C+Ly: 0.43±0.22; HSF: 1.54±0.32; HSF+Ly: 0.50±0.16). Tomato-oleoresin supplementation improved cardiac remodeling and dysfunction, cardiac inflammation and myocardial calcium kinetic. CONCLUSION: the anti-inflammatory effect of tomato-oleoresin supplementation treated the obesity-induced cardiac dysfunction by modulating myocardial calcium handling.

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.

Proteomic study of gamma-oryzanol preventive effect on a diet-induced non-alcoholic fatty liver disease model.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease associated with obesity and diabetes prevalence. The use of natural compounds has become an attractive approach to prevent NAFLD and its progression. Gamma-oryzanol (Orz) is a natural compound whose beneficial effects on chronic metabolic diseases have been reported. Therefore, we aimed to investigate the preventive effect of Orz on the hepatic proteome in a diet induced NAFLD model. Wistar rats were randomly distributed into three experimental groups (n=6/group) according to the diet received for 30 weeks: Control group, high sugar-fat (HSF) group, and HSF+Orz group. The isolated Orz was added to the chow at the dose of 0.5% (w/w). We evaluated the nutritional profile, characterized the presence of steatosis through histological analysis, triglyceride content in liver tissue and hepatic inflammation. Next, we performed label-free quantitative proteomics of hepatic tissue. Network analysis was performed to describe involved protein pathways. NAFLD induction was characterized by the presence of hepatic steatosis. Orz prevented lipid accumulation. The compound prevented alterations of the hepatic proteome, highlighted by the modulation of lipid metabolism, inflammation, oxidative stress, xenobiotic metabolism, and the sirtuin signaling pathway. It was possible to identify key altered pathways of NAFLD pathophysiology modulated by Orz which may provide insights into NAFLD treatment targets.

Effects of carnosine supplementation on markers for the pathophysiological development of metabolic dysfunction-associated steatotic liver disease in a diet-induced model.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

Role of sex and training characteristics on exercise effects on cardiovascular aging: protocol for a systematic review with meta-analysis of randomized trials.

BACKGROUND: Cardiovascular diseases remain a leading global cause of mortality worldwide especially in older adults. Although it is known that regular exercise reduces cardiovascular diseases incidence, its effects on specific cardiovascular aging parameters considering the influence of sex and different exercise designs are still not fully understood. Therefore, this systematic review and meta-analysis aims to evaluate the effects of different physical exercise protocols on age-related cardiovascular outcomes in older adults. METHODS: This systematic review and meta-analysis will be reported in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles will be eligible if they are randomized controlled trials with a primary objective of evaluating the chronic effects of exercise interventions on cardiovascular aging parameters. Search strategy will be performed from the inception to September 30th, 2023, in the following electronic databases: MEDLINE (Ovid), SCOPUS (Elsevier), Embase, Sport Discus (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection (Clarivate Analytics). Data will be extracted and managed through Research Electronic Data Capture (REDCap) software. The Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) will be used to assess the methodological quality of included studies. Additionally, the quality of the findings will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) profiler. Meta-analysis based on the random-effects model will be performed (if deemed suitable, considering the methodological and clinical heterogeneity of the studies) to estimate the effects of exercise training on cardiovascular aging variables (i.e., cardiac output; arterial stiffness; stroke volume; endothelial function; and carotid intima-media thickness). Heterogeneity will be assessed with the I2 statistics, while the publication bias will be assessed based on Egger's test. DISCUSSION: To the best of our knowledge, this will be the first systematic review and meta-analysis to investigate the impact of sex and training protocols on the cardiovascular aging parameters. Moreover, the findings of this systematic review and meta-analysis will provide evidence for health professionals in the management of elderly patients in order to optimize the exercise prescription to face the cardiovascular alterations related to the aging process, considering the effects of different protocols according to sex. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023441015 .

Treatment with bergamot (Citrus bergamia) leaves extract attenuates leptin resistance in obese rats.

Low-grade chronic inflammation in obesity is associated with leptin resistance. In order to alleviate this pathological condition, bioactive compounds capable of attenuating oxidative stress and inflammation have been researched, and bergamot (Citrus bergamia) presents these properties. The aim was to evaluate the effect of bergamot leaves extract on leptin resistance in obese rats. Animals were divided into 2 groups: control diet (C, n = 10) and high sugar-fat diet (HSF, n = 20) for 20 weeks. After detecting hyperleptinemia, animals were divided to begin the treatment with bergamot leaves extract (BLE) for 10 weeks: C + placebo (n = 7), HSF + placebo (n = 7), and HSF + BLE (n = 7) by gavage (50 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; adipose tissue dysfunction; inflammatory, oxidative markers and hypothalamic leptin pathway. HSF group presented obesity, metabolic syndrome, adipose tissue dysfunction, hyperleptinemia and leptin resistance compared to control group. However, the treated group showed a decrease in caloric consumption and attenuation of insulin resistance. Moreover, dyslipidemia, adipose tissue function, and leptin levels showed an improvement. At the level of the hypothalamus, the treated group showed a reduction of oxidative stress, inflammation and modulation of leptin signaling. In conclusion, BLE properties were able to improve leptin resistance through recovery of the hypothalamic pathway.

Oxidative stress evaluation in patients with chronic Chagas disease.

INTRODUCTION: Chagas disease (CD), caused by protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease that affects millions of people worldwide. The parasite clearance by the immune cells is accomplished by the activation of inflammation and production of reactive oxygen species, including nitric oxide (NO) that can lead to tissue injury and DNA damage. On the other hand, to balance the oxidative environment and decrease free radicals, there is an antioxidant system composed of enzymes and vitamins. The aim was to evaluate oxidative stress parameters in symptomatic and asymptomatic patients with Chagas disease. METHODS: Participants were divided into three groups: indeterminate CD (asymptomatic, n = 8), CD with cardiac/digestive involvement (symptomatic, n = 14), and Control healthy individuals (n = 20). The following parameters were analyzed: DNA damage, NO serum levels, hydrophilic antioxidant capacity (HAC) and vitamin E. RESULTS: Symptomatic patients showed increased DNA damage and NO levels and lower HAC and vitamin E levels compared to asymptomatic patients and control subjects. CONCLUSIONS: It is possible to conclude that CD patients with clinical symptoms have higher oxidative stress, characterized by increased DNA damage and NO levels, and reduced antioxidant capacity and vitamin E levels.

Fructose Consumption Alters Biogenic Amines Associated with Cardiovascular Disease Risk Factors. / Consumo de Frutose Altera Aminas Biogênicas Associadas a Fatores de Risco Cardiovasculares.

BACKGROUND: Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. OBJECTIVE: This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. METHODS: Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. RESULTS: Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. CONCLUSION: Fructose consumption alters BAs associated with CVD risk factors.

FUNDAMENTO: As doenças cardiovasculares (DCV) são a principal causa de mortalidade do mundo, e um de seus fatores de risco são os hábitos alimentares não saudáveis, tais como, o alto consumo de frutose. As aminas biogênicas (ABs) realizam funções importantes no corpo humano. Entretanto, o efeito do consumo de frutose nos níveis das ABs ainda não está claro, bem como a associação entre estes e os fatores de risco da DCV. OBJETIVO: Este estudo teve o objetivo de estabelecer a associação entre os níveis de ABs e os fatores de risco de DCV em animais que consumiram frutose. MÉTODOS: Ratos Wistar machos receberam ração convencional (n=8) ou ração convencional + frutose na água de beber (30%) (n=8) durante 24 semanas. Ao final, foram analisados os parâmetros nutricionais e da síndrome metabólica (SM) e os níveis plasmáticos das ABs. Foi adotado um nível de significância de 5%. RESULTADOS: O consumo de frutose levou à SM, reduziu os níveis de triptofano e 5-hidroxitriptofano e aumentou a histamina. Os níveis de triptofano, histamina e dopamina apresentaram correlação com parâmetros de síndrome metabólica. CONCLUSÃO: O consumo de frutose altera as ABs associadas a fatores de risco de doenças cardiovasculares.

Bergamot leaf extract treats cardiorenal metabolic syndrome and associated pathophysiological factors in rats fed with a high sugar fat diet.

Bergamot citrus (Citrus bergamia Risso et Poiteau), have been used as a strategy to prevent or treat comorbidities associated with metabolic syndrome parameters, such as cardiorenal metabolic syndrome (CRMS). The aim was to test the effect of bergamot leaf extract on CRMS and associated pathophysiological factors in rats fed with a high sugar-fat diet. Animals were divided into two experimental groups with control diet (Control, n = 30) and high sugar-fat diet (HSF, n = 30) for 20 weeks. Once CRMS was detected, animals were redivided to begin the treatment with Bergamot Leaf Extract (BLE) by gavage (50 mg/kg) for 10 weeks: control diet + placebo (Control, n = 09), control diet + BLE (Control + BLE, n = 09), HSF diet + placebo (HSF, n = 09), HSF + BLE (n = 09). Evaluation included nutritional, metabolic and hormonal analysis; and renal and cardiac parameters. HSF groups presented obesity, dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, insulin resistance. BLE showed protection against effects on hypertriglyceridemia, insulin resistance, renal damage, and structural and functional alterations of the heart. Conclusion: Bergamot leaf extract shows potential as a therapeutic to treat CRMS in animals fed with a high sugar-fat diet.

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.

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.

Antioxidant and anti-inflammatory properties of gamma- oryzanol attenuates insulin resistance by increasing GLUT- 4 expression in skeletal muscle of obese animals.

BACKGROUND: Skeletal muscle is the most important organ for whole-body glucose homeostasis. However, it has been suggested that obesity-related inflammation could be involved in insulin resistance and diabetes mellitus type 2 (DM2) development due several mechanisms, among them, the reduced expression of the glucose transporter type 4 (GLUT-4). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice that presents anti-inflammatory and antioxidant activities. The aim of this study was to verify if the effect antioxidant and anti-inflammatory of yOz attenuate insulin resistance in skeletal muscle of obese rats by increasing GLUT- 4 expression. METHODS: Male Wistar rats (±187 g) were initially randomly distributed into 2 experimental groups (control, n = 6, and high sugar-fat diet (HSF), n = 12) for 20 weeks. At week 20th of this study, once obesity and insulin resistance were detected in the HSF group, animals were divided to begin the treatment with γOz or continue receiving HSF for 10 more weeks. At the end it was analyzed nutritional, metabolic, inflammatory and oxidative stress parameters and GLUT-4 protein expression. RESULTS: The treatment improved insulin resistance, reduced inflammation, increased antioxidant response and GLUT-4 expression. CONCLUSION: It is possible to conclude that the antioxidant and anti-inflammatory activity of yOz attenuates insulin resistance by increasing GLUT-4 expression in skeletal muscle of obese animals.

Relationship between Innate Immune Response Toll-Like Receptor 4 (TLR-4) and the Pathophysiological Process of Obesity Cardiomyopathy. / Relação entre Resposta Imune Inata do Receptor Toll-Like-4 (TLR-4) e o Processo Fisiopatológico da Cardiomiopatia da Obesidade.

BACKGROUND: Obesity is a chronic low-grade inflammation condition related to cardiac disorders. However, the mechanism responsible for obesity-related cardiac inflammation is unclear. The toll-like receptor 4 (TLR-4) belongs to a receptor of the transmembrane family responsible for the immune response whose activation stimulates the production of proinflammatory cytokines. OBJECTIVE: To test whether the activation of the TLR-4 receptor participates in the obesity cardiomyopathy process, due to cytokine production through NF-ĸB activation. METHODS: Male Wistar rats were randomized into two groups: the control group (C, n= 8 animals) that received standard diet/water and the obese group (OB, n= 8 animals) that were fed a high sugar-fat diet and water plus 25% of sucrose for 30 weeks. Nutritional analysis: body weight, adiposity index, food, water, and caloric intake. Obesity-related disorders analysis: plasma glucose, uric acid and triglycerides, HOMA-IR, systolic blood pressure, TNF-α in adipose tissue. Cardiac analysis included: TLR-4 and NF-ĸB protein expression, TNF-α and IL-6 levels. Comparison by unpaired Student's t-test or Mann- Whitney test with a p-value < 0.05 as statistically significant. RESULTS: The OB group showed obesity, high glucose, triglycerides, uric acid, HOMA, systolic blood pressure, and TNF-α in adipose tissue. OB group presented cardiac remodeling and diastolic dysfunction. TLR-4 and NF-ĸB expression and cytokine levels were higher in OB. CONCLUSION: Our findings conclude that, in an obesogenic condition, the inflammation derived from cardiac TLR-4 activation can be a mechanism able to lead to remodeling and cardiac dysfunction.

FUNDAMENTO: A obesidade é uma condição inflamatória crônica de baixo grau relacionada a distúrbios cardíacos. No entanto, o mecanismo responsável pela inflamação cardíaca relacionada à obesidade não é claro. O receptor do tipo toll 4 (TLR-4) pertence a um receptor da família das transmembranas, responsável pela resposta imune, cuja ativação estimula a produção de citocinas pró-inflamatórias. OBJETIVO: Testar se a ativação do receptor TLR-4 participa do processo de cardiomiopatia da obesidade, devido à produção de citocinas por meio da ativação do NF-ĸB. MÉTODOS: Ratos Wistar machos foram randomizados em dois grupos: o grupo controle (C, n = 8 animais) que recebeu dieta padrão/água e o grupo obeso (OB, n = 8 animais) que foi alimentado com dieta rica em açúcar e gordura e água mais 25% de sacarose por 30 semanas. Análise nutricional: peso corporal, índice de adiposidade, alimentos, água e ingestão calórica. Análise de distúrbios relacionados à obesidade: glicose plasmática, ácido úrico e triglicerídeos, HOMA-IR, pressão arterial sistólica, TNF-α no tecido adiposo. A análise cardíaca incluiu: expressão das proteínas TLR-4 e NF-ĸB, níveis de TNF-α e IL-6. Comparação pelo teste t de Student não pareado ou teste de Mann-Whitney com um valor de p <0,05 como estatisticamente significativo. RESULTADOS: O grupo OB apresentou obesidade, glicose elevada, triglicerídeos, ácido úrico, HOMA, pressão arterial sistólica e TNF-α no tecido adiposo. O grupo OB apresentou remodelação cardíaca e disfunção diastólica. A expressão de TLR-4 e NF-ĸB e os níveis de citocinas foram maiores em OB. CONCLUSÃO: Nossos achados concluem que, em uma condição obesogênica, a inflamação derivada da ativação do TLR-4 cardíaco pode ser um mecanismo capaz de levar à remodelação e disfunção cardíaca.

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.

Consumo de Frutose Altera Aminas Biogênicas Associadas a Fatores de Risco Cardiovasculares / Fructose Consumption Alters Biogenic Amines Associated with Cardiovascular Disease Risk Factors

Resumo Fundamento As doenças cardiovasculares (DCV) são a principal causa de mortalidade do mundo, e um de seus fatores de risco são os hábitos alimentares não saudáveis, tais como, o alto consumo de frutose. As aminas biogênicas (ABs) realizam funções importantes no corpo humano. Entretanto, o efeito do consumo de frutose nos níveis das ABs ainda não está claro, bem como a associação entre estes e os fatores de risco da DCV. Objetivo Este estudo teve o objetivo de estabelecer a associação entre os níveis de ABs e os fatores de risco de DCV em animais que consumiram frutose. Métodos Ratos Wistar machos receberam ração convencional (n=8) ou ração convencional + frutose na água de beber (30%) (n=8) durante 24 semanas. Ao final, foram analisados os parâmetros nutricionais e da síndrome metabólica (SM) e os níveis plasmáticos das ABs. Foi adotado um nível de significância de 5%. Resultados O consumo de frutose levou à SM, reduziu os níveis de triptofano e 5-hidroxitriptofano e aumentou a histamina. Os níveis de triptofano, histamina e dopamina apresentaram correlação com parâmetros de síndrome metabólica. Conclusão O consumo de frutose altera as ABs associadas a fatores de risco de doenças cardiovasculares.

Abstract Background Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. Objective This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. Methods Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. Results Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. Conclusion Fructose consumption alters BAs associated with CVD risk factors.

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.

Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III Protein Expression

Abstract Background: As some individuals present resistance to obesity development, experiments have been trying to understand their susceptibility to cardiometabolic diseases. Objetive: To evaluate if the cardiac remodeling was related to collagen protein expression change. Methods: Male Wistar rats were randomized into two experimental groups: control diet (CD, n=15) or high-fat diet (HFD, n=15) for 30 weeks. Rats fed with HFD were ranked based on their adiposity indexes and classified as obese (Ob, n = 8) or obesity-resistant (ROb, n = 6). Rats that failed to present the normal characteristic of the control group while fed with CD were excluded (Control, n = 8). Nutritional profile, comorbidities (dyslipidemia, hypertension, glucose metabolism, hyperleptinemia), cardiac remodeling, and collagen protein expression were evaluated. The groups were compared by One-Way ANOVA, together the Tukey post hoc test, with p<0.05 considered significant. Results: The Ob rats presented an increased adiposity index when compared to C and ROb. Both groups Ob and ROb presented increased low-density lipoprotein (LDL), insulin, homeostatic model assessment of insulin resistance (HOMA- IR) and systolic blood pressure (SBP), and low high-density lipoprotein (HDL) levels when compared to the control group. The levels of triglycerides, non-esterified fatty acid (NEFA), and leptin were lower in ROb as compared to Ob, but higher than the control group. The Ob and ROb groups presented cardiac remodeling, evidenced by echocardiographic and post-mortem analysis. The collagen protein expression did not differ among the groups. Conclusion: The ROb animals present cardiac remodeling that is not related to collagen type I and III protein expression change.