Beverages Rich in Resveratrol and Physical Activity Attenuate Metabolic Changes Induced by High-Fat Diet.

Consumption of saturated fat causes deleterious effects on health, which could be minimized through physical activity and foods with functional characteristics consumption. The aim of the study was to evaluate the beverage rich in resveratrol consumption and physical exercise in gut microbiota, body composition, lipid peroxidation, interleukin-6 (IL6) concentration and systolic blood pressure (SBP) of rats to the high-fat diet. Wistar rats were fed with control diet, high-fat diet (HFD), HFD and 15 mL solution of resveratrol, HFD and 15 mL of grape juice, HFD and 10 mL of red wine. All animals performed the physical training protocol five days a week. Grape juice and red wine composition were analyzed, SBP, body mass, consumption, adiposity and body composition, gut microbiota, lipid peroxidation and inflammation were evaluated. The grape juice (114.8 ± 22.5 mmHG) and red wine (129 ± 15.8 mmHg) groups showed lower SBP when compared to HFD (216.8 ± 20.6 mmHg) (p < 0.0001). The grape juice group (GJG) (39.1 ± 7) had a higher number of microbiota bands DNA when compared to the other groups (p = 0.002). The GJG (33.7 ± 6.7 pg/mL) presented lower concentration IL6 when compared to high-fat group (47.3 ± 16 pg/mL) (p = 0.003). GJG (4.7 ± 1.2 nmol/L) presented a lower concentration of TBARS when compared to control group (6.1 ± 1.4 nmol/L) and resveratrol group (6.6 ± 0.9 nmol/L), and the red wine group (7.4 ± 1.2 nmol/L) had a higher concentration of TBARS when compared to control group and GJG (p = 0.0001). The consumption of these beverages, especially grape juice, together with physical exercise, was able to promote beneficial changes even in the presence of a HFD.

Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?

BACKGROUND: Trimethylamine N-oxide (TMAO) is a metabolite that has attracted attention due to its positive association with several chronic non-communicable diseases such as insulin resistance, atherosclerotic plaque formation, diabetes, cancer, heart failure, hypertension, chronic kidney disease, liver steatosis, cardiac fibrosis, endothelial injury, neural degeneration and Alzheimer's disease. TMAO production results from the fermentation by the gut microbiota of dietary nutrients such as choline and carnitine, which are transformed to trimethylamine (TMA) and converted into TMAO in the liver by flavin-containing monooxygenase 1 and 3 (FMO1 and FMO3). Considering that TMAO is involved in the development of many chronic diseases, strategies have been found to enhance a healthy gut microbiota. In this context, some studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota and possibly reduce TMAO production. OBJECTIVE: This review has as main objective to discuss the studies that demonstrated the effects of food on the reduction of this harmful metabolite. METHODS: All relevant articles until November 2020 were included. The articles were searched in Medline through PubMed. RESULTS: Both the food is eaten acutely and chronically, by altering the nature of the gut microbiota, influencing colonic TMA production. Furthermore, hepatic production of TMAO by the flavin monooxygenases in the liver may also be influenced by phenolic compounds present in foods. CONCLUSION: The evidence presented in this review shows that TMAO levels can be reduced by some bioactive compounds. However, it is crucial to notice that there is significant variation among the studies. Further clinical studies should be conducted to evaluate these dietary components' effectiveness, dose, and intervention time on TMAO levels and its precursors.

Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them?

Recent studies have suggested that uremic toxins such as indoxyl sulfate (IS) and indole-3-acetic acid (IAA) from the metabolism of the gut microbiota may be involved in the inflammatory signaling pathway in chronic kidney disease (CKD) patients through the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The objective of this study was to investigate the possible relationship between uremic toxins (IS and IAA) and AhR protein expression in CKD patients. A cross-sectional observational study involving 17 hemodialysis (HD) [11 men, 55.5 ± 11.7 years of age, 54.0 (25.5-136.0) months of HD, body mass index (BMI) of 25.8 ± 3.8 kg/m2] and 15 non-dialysis-dependent (NDD) CKD (8 men, 54.1 ± 18.2 years of age, glomerular filtration rate of 34.8 ± 21.0 mL/min/1.73 m2, BMI of 27.4 ± 5.0 kg/m2) patients was conducted. IS and IAA levels were measured by reversed-phase high-performance liquid chromatography, and the protein expression levels of AhR and nuclear factor κ B (NF-κB) were evaluated by a Western blot assay. There was no difference in the expression of either AhR or NF-κB in the patients, and as expected, uremic toxin levels were higher in HD patients than in NDD patients. In the overall analysis, AhR protein expression was positively associated with IAA plasma levels ( r = 0.4; p = 0.03) and NF-κB protein expression ( r = 0.62; p = 0.001). Although the role of AhR in inflammation and CVD in CKD patients is far from being completely understood, the association between IAA and AhR observed in this study suggests a possible role for uremic toxins in the cell signaling pathway involved in inflammation in CKD patients.

Indoxyl sulfate and p-cresyl sulfate in chronic kidney disease. Could these toxins modulate the antioxidant Nrf2-Keap1 pathway?

Protein-bound uremic toxins (i.e., indoxyl sulfate or p-cresyl sulfate), produced by intestinal bacteria, are accumulated in the plasma of chronic kidney disease (CKD) patients. These toxins interact negatively with biological functions, having potent oxidative stress-inducing effects and a pathological effect on cardiovascular disease. Recent research in CKD has shown that oxidative stress and inflammation can be compounded by impaired activation of the nuclear factor (erythroid-2-related factor)-2 (Nrf2)-Kelch-like ECH associating protein-1 (Keap1) pathway, a major cellular defense mechanism. However, to date, many questions arise regarding the role of this system in CKD. For example, protein-bound uremic toxins promote oxidative stress in CKD patients, but their putative effect on the Nrf2-Keap1 system has yet to be examined in these patients. This review will focus on the putative relationship among protein-bound uremic toxins, oxidative stress, and a possible decreased expression of Nrf2 in CKD.

Is the enteric nervous system a lost piece of the gut-kidney axis puzzle linked to chronic kidney disease?

The enteric nervous system (ENS) regulates numerous functional and immunological attributes of the gastrointestinal tract. Alterations in ENS cell function have been linked to intestinal outcomes in various metabolic, intestinal, and neurological disorders. Chronic kidney disease (CKD) is associated with a challenging intestinal environment due to gut dysbiosis, which further affects patient quality of life. Although the gut-related repercussions of CKD have been thoroughly investigated, the involvement of the ENS in this puzzle remains unclear. ENS cell dysfunction, such as glial reactivity and alterations in cholinergic signaling in the small intestine and colon, in CKD are associated with a wide range of intestinal pathways and responses in affected patients. This review discusses how the ENS is affected in CKD and how it is involved in gut-related outcomes, including intestinal permeability, inflammation, oxidative stress, and dysmotility.

Brazil Nut-Enriched Diet Modulates Enteric Glial Cells and Gut Microbiota in an Experimental Model of Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.

Is there association between uric acid and inflammation in hemodialysis patients?

BACKGROUND: Elevated serum uric acid has been associated with a variety of cardiovascular disease and with inflammation, but these have been little explored in chronic kidney disease (CKD). Elevated uric acid levels are common in CKD patients and could be involved in inflammatory milieu; our aim was to analyze the association between uric acid and inflammatory markers in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from private clinic, Rio de Janeiro, Brazil. PATIENTS: This study included 50 HD patients and 21 healthy subjects. METHODS AND PROCEDURES: This study included 50 HD patients [62% men, 54.3 ± 12.6 years, 57.5 ± 50.1 months on dialysis, and body mass index (BMI), 24.4 ± 4.1 kg/m2] and 21 healthy individuals (45% men, 50.7 ± 15.7 years and BMI, 25.5 ± 4 kg/m2). Uric acid was measured using uricase-PAP method; inflammatory [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)] and atherosclerosis markers [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1)] were measured by a multiplexed assay. RESULTS: PATIENTS presented high levels of TNF-α, IL-6, CRP, VCAM-1, ICAM-1 (5.5 ± 2.1 pg/mL, 4.1 ± 1.6 pg/mL, 0.32 ± 0.30 mg/mL, 48.5 ± 8.5 ng/mL, 20.5 ± 15.9 ng/mL, respectively), compared with healthy individuals (2.4 ± 1.1 pg/mL, 2.7 ± 0.4 pg/mL, 0.11 ± 0.12 mg/mL, 23.8 ± 5.5 ng/mL, 7.2 ± 1.2 ng/mL, respectively) ( p < 0.04). Uric acid levels were also higher in HD patients (5.4 ± 1.3 mg/dL) than in healthy individuals (3.9 ± 0.9 mg/dL) ( p < 0.02). There was a positive correlation between uric acid and inflammatory markers, IL-6 (r = 0.30, p = 0.01), CRP (r = 0.37, p = 0.003), TNF-α (r = 0.40, p = 0.001), ICAM-1 (r = 0.53, p = 0.0001), and VCAM-1 (r = 0.45, p = 0.0001). CONCLUSION: These original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients. However, further prospective studies involving intervention trials should be conducted in order to search for actual causality relationship between these markers.

Reduced plasma zinc levels, lipid peroxidation, and inflammation biomarkers levels in hemodialysis patients: implications to cardiovascular mortality.

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(-)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m(2)) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m(2)) and followed for 24 months to investigate the risks for CV mortality. LDL(-) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 µg/dL) and high-LDL(-) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4µ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = -0.49; p = 0.0001) and LDL(-) (r = -0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.

Effects of Probiotic-Enriched Minas Cheese (Lactobacillus acidophilus La-05) on Cardiovascular Parameters in 5/6 Nephrectomized Rats.

Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.

Relaxing the "second brain": nutrients and bioactive compounds as a therapeutic and preventive strategy to alleviate oxidative stress in the enteric nervous system.

The enteric nervous system (ENS) regulates several functional and immunological processes in the gastrointestinal tract. However, some diseases can disrupt the ENS functionality, impacting the behavior of enteric neurons and enteric glial cells by increasing the accumulation of reactive oxygen species. Oxidative stress is considered to be a trigger for alterations in these cells' morphology, density, and neurochemical patterns. In light of this, nutritional strategies are a growing field of investigation regarding their potential to modulate enteric neurons and enteric glial cells through reduced reactive oxygen species production. Moreover, several lines of evidence show that nutrients are related to counteracting oxidative stress. Some studies have evaluated the potential of nutrients with antioxidant roles (such as amino acids, polyphenols, prebiotics, vitamins, and specific extracts obtained from foods) to modulate the ENS. Thus, this review discusses how bioactive compounds and nutrients can impact the ENS by alleviating oxidative stress.

High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility.

Obesity is a chronic disease that affects various physiological systems. Among them, the gastrointestinal tract appears to be a main target of this disease. High-fat diet (HFD) animal models can help recapitulate the classic signs of obesity and present a series of gastrointestinal alterations, mainly dysmotility. Because intestinal motility is governed by the enteric nervous system (ENS), enteric neurons, and glial cells have been studied in HFD models. Given the importance of the ENS in general gut physiology, this review aims to discuss the relationship between HFD-induced neuroplasticity and gut dysmotility observed in experimental models. Furthermore, we highlight components of the gut environment that might influence enteric neuroplasticity, including gut microbiota, enteric glio-epithelial unit, serotonin release, immune cells, and disturbances such as inflammation and oxidative stress.

Brazil nut supplementation does not affect trimethylamine-n-oxide plasma levels in patients with coronary artery disease.

The purposes of this study were to assess the effect of Brazil nut supplementation on trimethylamine N-oxide (TMAO) levels and glutathione peroxidase (GPx) activity in patients with coronary artery disease (CAD). Patients with CAD were randomly assigned to two groups, Brazil nut group (23 patients, 48% male, 62.7 ± 6.8 years, 29.4 ± 5.8 kg/m2 ), which received one Brazil nut per day for 3 months, and the control group (14 patients, 43% male, 63.7 ± 8.7 years, 28.4 ± 4.2 kg/m2 ) who did not receive any supplementation. After 3 months, TMAO levels and their precursors did not change in either group. Although not significant, GPx activity increased by 41% in the Brazil nut group. TMAO levels were negatively associated with total fiber intake (r = -0.385 and p = .02). A 3-month Brazil nut supplementation did not change TMAO levels and GPx activity in CAD patients. PRACTICAL APPLICATIONS: Trimethylamine N-oxide (TMAO) has been associated with oxidative stress and cardiovascular disease risk. Thus, the increase in antioxidants enzymes production could be a promising strategy to reduce TMAO-mediated oxidative stress. In this context, nutritional strategies are well-known as activators of cellular antioxidant responses. As Brazil nuts have a known role in reducing oxidative stress by increasing glutathione peroxidase (GPx) activity (a selenium-dependent antioxidant enzyme), this study hypothesized that Brazil nuts could be a strategy that, via antioxidant capacity, would reduce TMAO plasma levels. Although no changes in TMAO levels and GPx activity can be observed in this study, it is believed that other results can be obtained depending on the dosage used. Thus, this study can open new paths and direct other studies with different doses and treatment times to evaluate the effects of Brazil Nuts on TMAO levels.

Supplementation of diet with Brazil nut modulates body composition, bone parameters, and lipid peroxidation in Wistar rats.

Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p  < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.

Brazil Nut (Bertholletia excelsa H.B.K) Retards Gastric Emptying and Modulates Enteric Glial Cells in a Dose-Dependent Manner.

BACKGROUND: The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. OBJECTIVE: The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. METHODS: Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. RESULTS: The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). CONCLUSION: The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.

Brazil Nut Supplementation Does Not Regulate PPARß/δ Signaling Pathway in Peripheral Blood Mononuclear Cells from Coronary Artery Disease Patients.

Background: Peroxisome proliferator-activated receptor (PPAR)ß/δ activation is a potential target for modulation of inflammation in cardiovascular disease. PPARß/δ activation depends on the presence of a ligand, which may be pharmacological or natural, such as bioactive compounds and nutrients. Due to its composition, rich in selenium and unsaturated fatty acids, Brazil nuts have been related to reduced oxidative stress and inflammation in chronic non-communicable diseases and could regulate PPARß/δ. This study aimed to evaluate the effects of Brazil nut supplementation on PPARß/δ mRNA expression in patients with Coronary Artery Disease (CAD).Methods: A secondary analysis of a randomized controlled clinical trial was performed with 36 CAD patients. Patients were randomly assigned to either the Supplementation group or the control group and followed up for three months. The Supplementation group consumed 1 Brazil nut/day; the control group did not receive any intervention. At the baseline and after three months, analysis of gene expression and biochemical parameters linked to inflammatory biomarkers and oxidative stress was carried out.Results: In the supplementation group, no significant change was observed in PPARß/δ (0.9 ± 0.5 vs 1.2 ± 0.6; p = 0.178) and NF-κB (1.6 ± 1.5 vs 0.8 ± 0.30, p = 0.554) mRNA expression. There were no significant changes in both groups concerning all the other biochemical parameters.Conclusion: One Brazil nut per day for three months was not able to increase the PPARß/δ expression in CAD patients.

Consumption of oils and anthocyanins may positively modulate PPAR-γ expression in chronic noncommunicable diseases: A systematic review.

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a central role in health and is an essential cardioprotective factor because of its effect on lipid and glucose metabolism, inflammation, and oxidative stress. We hypothesized that nutritional strategies positively regulate PPAR-γ expression in patients with noncommunicable diseases (NCDs). A systematic search was conducted using PubMed, Scientific Electronic Library Online (SciELO), and LILACS databases from May 2020 to January 2021. Eligibility criteria included placebo-controlled randomized clinical trials in adults with chronic diseases involving nutritional strategies, which performed PPAR-γ analysis (majority on mononuclear cells) before and after the intervention. The exclusion criteria included studies published more than 10 years ago, studies not published in English or Spanish, theses, reviews, and other study designs. The review was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality was assessed based on 7 criteria obtained from the Cochrane Handbook. A total of 7 studies were included that reported the effects of different nutritional strategies (such as anthocyanins, fish oil, Berberis vulgaris juice, ketogenic diet, flaxseed oil, olive oil) on 346 patients with NCDs (such as type 2 diabetes, hypertension, obesity, and cancer) between 18 and 85 years of age. These results suggest that anthocyanins, flaxseed oil, and olive oil may function as putative PPAR-γ agonists.

5/6 nephrectomy affects enteric glial cells and promotes impaired antioxidant defense in the colonic neuromuscular layer.

AIMS: Chronic kidney disease (CKD) produces multiple repercussions in the gastrointestinal tract (GIT), such as alterations in motility, gut microbiota, intestinal permeability, and increased oxidative stress. However, despite enteric glial cells (EGC) having important neural and immune features in GIT physiology, their function in CKD remains unknown. The present study investigates colonic glial markers, inflammation, and antioxidant parameters in a CKD model. MAIN METHODS: A 5/6 nephrectomized rat model was used to induce CKD in rats and Sham-operated animals as a control to suppress. Biochemical measures in plasma and neuromuscular layer such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were carried out. Kidney histopathology was evaluated. Colon morphology analysis and glial fibrillary acid protein (GFAP), connexin-43 (Cx43), nuclear factor-kappa B (NF-κB) p65, and GPx protein expression were performed. KEY FINDINGS: The CKD group exhibited dilated tubules and tubulointerstitial fibrosis in the reminiscent kidney (p = 0.0002). CKD rats showed higher SOD activity (p = 0.004) in plasma, with no differences in neuromuscular layer (p = 0.9833). However, GPx activity was decreased in the CKD group in plasma (p = 0.013) and neuromuscular layer (p = 0.0338). Morphological analysis revealed alterations in colonic morphometry with inflammatory foci in the submucosal layer and neuromuscular layer straightness in CKD rats (p = 0.0291). In addition, GFAP, Cx43, NF-κBp65 protein expression were increased, and GPx decreased in the neuromuscular layer of the CKD group (p < 0.05). SIGNIFICANCE: CKD animals present alterations in colonic cytoarchitecture and decreased layer thickness. Moreover, CKD affects the enteric glial network of the neuromuscular layer, associated with decreased antioxidant activity and inflammation.

Impact of Brazil Nut (Bertholletia excelsa, H.B.K.) Supplementation on Body Composition, Blood Pressure, and the Vascular Reactivity of Wistar Rats When Submitted to a Hypersodium Diet.

Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis.Objective: The aim of this study was to investigate the impact of Brazil nut (Bertholletia excelsa, H.B.K.) (BN) supplementation (10% in chow, wt/wt) on the vascular reactivity of Wistar rats during chronic exposure to a sodium overload (1% in water).Methods: First, male Wistar rats were allocated into two groups: Control Group (CG) and the Hypersodic Group (HG) for 4 weeks. Afterward, the CG was divided into the Brazil Nut Group (BNG) and the HG Group into the Hypersodic Brazil Nut Group (HBNG) for a further 8 weeks, totaling 4 groups. Blood pressure was measured during the protocol. At the end of the protocol, the vascular reactivity procedure was performed. Glucose, lipid profile, lipid peroxidation, and platelet aggregation were analyzed in the serum. Body composition was determined by the carcass technique.Results: The groups that were supplemented with the BN chow presented less body mass gain and body fat mass, together with lower serum glucose levels. The HG Group presented an increase in blood pressure and a higher platelet aggregation, while the BN supplementation was able to blunt this effect. The HG Group also showed an increase in contractile response that was phenylephrine-induced and a decrease in maximum relaxation that was acetylcholine-induced when compared to the other groups.Conclusion: The BN supplementation was able to prevent an impaired vascular function in the early stages of arterial hypertension, while also improving body composition, serum glucose, and platelet aggregation.

Nrf2, NF-κB and PPARß/δ mRNA Expression Profile in Patients with Coronary Artery Disease.

BACKGROUND: Oxidative stress and inflammation are present in coronary artery disease (CAD) and are linked to the activation of the transcription nuclear factor kappa B (NF-κB). To attenuate these complications, transcription factors like nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) can be activated to inhibit NF-κB. However, the available data on expression of NF-κB, Nrf2 and PPARß/δ in CAD patients are limited. OBJECTIVE: To evaluate the expression of the transcription factors NF-κB and Nrf2 and PPAR𝛽/𝛿 in CAD patients. METHODS: Thirty-five patients (17 men, mean age 62.4 ? 7.55 years) with CAD and twelve patients (5 men, mean age 63.50 ? 11.46 years) without CAD were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and processed for mRNA expression of Nrf2, NF-κB, NADPH: quinone oxidoreductase 1 (NQO1) and PPARß/δ mRNAs using quantitative real-time polymerase chain reaction (qPCR). p < 0.05 was considered statistically significant. RESULTS: There was no difference in the mRNA expressions of Nrf2 (1.35 ? 0.57), NF-κB (1.08 ? 0.50) or in the antioxidant enzyme NQO1 (1.05 ? 0.88) in the CAD group compared to the group without CAD (1.16 ? 0.76, 0.95 ? 0.33, 0.81 ? 0.55, respectively). However, PPARß/δ was highest expressed in the CAD group (1.17 ? 0.86 vs. 0.56 ? 0.34, p = 0.008). CONCLUSION: The main finding of this study was the PPARß/δ being more expressed in the PBMC of patients with CAD compared to the control group, whereas no differences were observed in Nrf2 or NF-κB mRNA expressions.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.