Ludmila F. M. F. Cardozo

Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2

The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2-Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health.

Maternal flaxseed diet during lactation alters milk composition and programs the offspring body composition, lipid profile and sexual function

We evaluated the effects of maternal dietary flaxseed during lactation on milk composition, body composition and sexual function of the adult female offspring. The dams were fed a control casein diet (C) or flaxseed diet (F, 25%) throughout lactation. F mothers showed higher serum 17beta-estradiol (E2) and leptin at weaning. F mothers milk had lower total cholesterol (TC) and higher E2 and leptin. The offspring of F dams showed lower body mass (BM), body fat mass (BFM), visceral fat mass (VFM), TC and triglycerides (TG) and higher serum leptin and E2 at 21 days. F offspring showed delayed puberty onset. At 150 days, these offspring presented higher BFM, VFM, TC, TG, E2 and lower relative uterine weight and lower progesterone. In conclusion, flaxseed during lactation did affect the lipid profile, adipose tissue and sexual function in adulthood, probably due hyperestrogenism and hyperleptinemia at weaning.

Impact of flaxseed intake upon metabolic syndrome indicators in female Wistar rats

PURPOSE To evaluate whether the prolonged consumption of flaxseed minimize the factors that trigger MS in healthy rats. METHODS Pregnant rats were divided immediately after delivery into two groups during the lactation period, a control group (CG) receiving casein-based diet with 17% of protein, and a Flaxseed group (FG) with casein-based diet plus 25% of flaxseed. At weaning, 12 offspring of each group continued to receive the same feed but with 10% of protein up to 200 days old. RESULTS FG showed a significant reduction in body weight (p=0.001), total cholesterol levels (p<0.0001), triglycerides (p=0.0001), and glucose (p=0.001). CONCLUSION The flaxseed alters the indicators related to development of metabolic syndrome, because it has beneficial effects on lipids and glucose profiles and prevents the excess of body weight gain.

Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients

Background Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly related to the increased risk of developing cardiovascular disease, which is the major cause of death in these patients, particularly for those undergoing hemodialysis (HD). Strength physical exercise is a new therapeutic approach to reduce these complications in CKD patients. Following this, the purpose of this study was to assess the effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in HD patients. Methods Sixteen HD patients were studied (11 women; 44.4±14.6 years; body mass index 23.3±4.9 kg/m2; 61.6±43.1 months of dialysis) and served as their own controls. Acute (single session) intradialytic physical exercise were performed at 60% of the one-repetition maximum test for three sets of 10 repetitions for four exercise categories in both lower limbs during 30 minutes. Blood samples were collected on two different days at exactly the same time (30 minutes and 60 minutes after initiating the dialysis—with and without exercise). Antioxidant enzymes activity [superoxide dismutase (SOD), catalase, and glutathione peroxidase], lipid peroxidation marker levels (malondialdehyde), and inflammatory marker levels (high-sensitivity C-reactive protein) were determined. Results SOD plasma levels were significantly reduced after acute physical exercise from 244.8±40.7 U/mL to 222.4±28.9 U/mL (P=0.03) and, by contrast, increased on the day without exercise (218.2±26.5 U/mL to 239.4±38.6 U/mL, P=0.02). There was no alteration in plasma catalase, glutathione peroxidase, malondialdehyde, or high-sensitivity C-reactive protein levels in on either day (with or without exercise). Additionally, there was no association between these markers and clinical, anthropometric, or biochemical parameters. Conclusion These data suggest that acute intradialytic strength physical exercise was unable to reduce oxidative stress and inflammation, and in addition, it seems to reduce plasma SOD levels, which could exacerbate the oxidative stress in HD patients.

Maternal consumption of flaxseed during lactation affects weight and hemoglobin level of offspring in rats

OBJECTIVE: To investigate the effects of maternal flaxseed consumption during lactation on the body weight, hematological indicators and visceral fat mass of male offspring in adulthood. METHODS: Sixteen female Wistar rats were divided into two groups after giving birth. During lactation the control group (CG) was fed a casein-based diet and the flaxseed group (FG) was fed a casein-based diet containing 25% flaxseed. After weaning, male offspring were fed on commercial chow until adulthood and euthanized at 170 days for blood collection and visceral fat mass assessment. RESULTS: Offspring of rats in the FG had lower body weight (FG = 42.69±3.06 g; CG = 47.31±4.72 g; p = 0.036) at weaning. At 170 days, lower hemoglobin levels were observed in the FG (FG = 12.30±1.28 g/dL; CG = 13.88±0.91 g/dL; p = 0.02). There was no statistically significant difference in visceral fat mass between groups. CONCLUSIONS: Maternal consumption of a flaxseed-based diet during lactation resulted in lower body weight at weaning and lower hemoglobin levels in adulthood, when compared with the control group.

Prolonged consumption of flaxseed flour increases the 17β-estradiol hormone without causing adverse effects on the histomorphology of Wistar rats' penis.

Consumption of foods rich in phytoestrogens such as flaxseed has increased due to its chemoprotective effects, especially those related to the cardiovascular system. The flaxseed has components that can interfere with development of male reproductive system. This study aims to investigate the possible effects of prolonged consumption of flaxseed flour on hormonal and histomorphologic penis parameters of adult Wistar rats. Rat dams were divided into two groups during lactation period: the control group that was fed with diet based on casein and the flaxseed group that was fed with diet based on casein containing 25% of flaxseed . At weaning, 10 male offspring from each group continued to receive the experimental diets until 250 days old. Rats fed with diet containing flaxseed showed increased concentrations of 17β-estradiol (p=0.01) but no changes in testosterone concentrations. With regard to histomorphometric analysis of the penis, supplemented rats had lower values for the total area of the corpus spongiosum (p=0.01). All other analyzed parameters wer e similar as the control. Results showed that the use of flaxseed flour did not cause adverse effects on the penis morphology but increases the 17β-estradiol hormone, when consumed in integral form for a prolonged period.

Red meat intake in chronic kidney disease patients: Two sides of the coin

Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate. These uremic toxins are associated with increased risk for cardiovascular (CV) mortality. Limiting the intake of red meat in patients with chronic kidney disease (CKD) thus may be a good strategy to reduce CV risk, and may slow the progression of kidney disease. In the present review, we discuss the role of red meat in the diet of patients with CKD. Additionally, we report on a pilot study that focused on the effect of a low-protein diet on TMAO plasma levels in nondialysis CKD patients.

Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD‐MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p‐cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease.

Prolonged flaxseed flour intake decreased the thickness of the aorta and modulates some modifiable risk factors related to cardiovascular disease in rats

UNLABELLED Cardiovascular diseases are a major public health problem. Different risk factors have been recognized as the main causes of the development and progression of cardiovascular diseases. Flaxseed is a source of dietary fiber, lignans, and alpha-linolenic acid. The aim of this study was to evaluate the effects of prolonged supplementation with flaxseed flour as preventive therapy on cardiovascular risk parameters in healthy Wistar rats. MATERIAL AND METHODS Female Wistar rats were divided into two groups after giving birth and during lactation period: the control group was fed with diet based on casein and the flaxseed group was fed with diet based on casein containing 25% of flaxseed flour. At weaning, 10 male offspring from each group continued to receive the same diets from their mothers during 250 days. The body weight, visceral fat mass, cholesterol, triglycerides, HDL, VLDL, glucose and thickness of the aorta were analyzed. RESULTS The body weight, visceral fat mass, cholesterol, triglycerides, HDL, VLDL, glucose and thickness of the aorta values were statistically lower when compared to control group. CONCLUSION The data suggest that flaxseed flour supplementation in healthy wistar rats for a prolonged period may decrease the thickness of the aorta and may be used as a preventive measure in modulating some modifiable risk factors related to cardiovascular disease.

Could physical exercises modulate Nrf2-Keap1 pathway in chronic kidney disease?

Patients with chronic kidney disease (CKD) have various metabolic disorders caused by a chronic state of oxidative stress and inflammation, and recently, nuclear factor-erythroid 2-related factor 2 (Nrf2) has emerged as a factor that plays a significant role in cellular protection against oxidative stress and inflammation. This transcription factor when activated can regulate antioxidant and anti-inflammatory cellular responses leading to the expression of detoxifying enzymes. Studies have shown that Nrf2 expression can be modulated by several factors, such as bioactive compounds and physical exercise. In fact, exercise in CKD patients can bring many benefits; however, there are no studies correlating physical activity and Nrf2 expression in CKD patients. This review aims to discuss whether there is any evidence to justify a recommendation of physical exercise in CKD patients as a non-pharmacological option to activate the Nrf2 pathway.