RESUMO
Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.
Assuntos
Mirtilos Azuis (Planta) , Fragaria , Microbioma Gastrointestinal , Insuficiência Renal Crônica , Rubus , Vaccinium macrocarpon , Animais , Humanos , Frutas , Disbiose , Qualidade de Vida , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/microbiologiaRESUMO
AIMS: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases. MAIN METHODS: The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect. KEY FINDINGS: Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I2 = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I2 = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I2 = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I2 = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I2 = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I2 = 0 %). SIGNIFICANCE: These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.
Assuntos
Nefropatias , Fator 2 Relacionado a NF-E2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Creatinina , Fator 2 Relacionado a NF-E2/metabolismo , Nefropatias/tratamento farmacológico , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Biomarcadores/metabolismoRESUMO
Food nutrients and bioactive compounds have been widely explored due to the increased prevalence of chronic non-communicable diseases. Antioxidant supplementation might be a crucial non-pharmacological strategy against oxidative stress. However, although some assays evaluate the antioxidant potential of a particular food or food compound, in vivo responses related to oxidative stress in the body may not be reproduced or directly correlated with in vitro values. Therefore, this review aims to discuss the relationship between data obtained in vitro for the antioxidant potential of food/food compounds and the effects observed in vivo. More specifically, we examined in vitro methods for evaluating antioxidant potential, their limitations, and the effects of consuming food rich in antioxidants on oxidative stress biomarkers. This review will help to understand the effects of antioxidant compounds on oxidative stress biomarkers (usually measured in vivo) and their use as health parameters to explain the effects of dietary antioxidants.
Assuntos
Antioxidantes , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Dieta , Biomarcadores , NutrientesRESUMO
The peroxisome proliferator-activated receptor (PPAR) ß/δ has an important role in multiple inflammatory conditions, including obesity, hypertension, cancer, cardiovascular disease, diabetes mellitus, and autoimmune diseases. PPARß/δ forms a heterodimer with the retinoic acid receptor and binds to peroxisome proliferator response elements to initiate transcription of its target genes. PPARß/δ is also able to suppress the activities of several transcription factors, including nuclear factor κB, and activator protein 1, thus regulating anti-inflammatory cellular responses and playing a protective role in several diseases. Recent studies have shown that nutritional compounds, including nutrients and bioactive compounds, can regulate PPARß/δ expression. This review discusses key nutritional compounds that are known to modulate PPARß/δ and are likely to affect human health.
Assuntos
Dieta , Inflamação/metabolismo , PPAR delta/metabolismo , PPAR beta/metabolismo , Animais , Curcumina/farmacologia , Flavonoides/farmacologia , Humanos , Inflamação/dietoterapia , NF-kappa B/metabolismo , PPAR delta/efeitos dos fármacos , PPAR beta/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Receptores do Ácido Retinoico/metabolismo , Vitamina A/farmacologiaRESUMO
An imbalance of gut microbiota is considered a new cardiovascular risk factor for chronic kidney disease (CKD) patients, since it is directly associated with increased uremic toxin production, inflammation and oxidative stress. Strategies such as prebiotic supplementation have been suggested to mitigate these complications. We hypothesized that prebiotic-resistant starch could ameliorate uremic toxins levels, oxidative stress, and inflammatory states in hemodialysis (HD) patients. This pilot study evaluated 31 HD patients assigned to either resistant starch (16 g of resistant starch Hi-Maize® 260) or placebo (manioc flour) supplementation, which they received for 4 weeks on alternate days through cookies on dialysis days and powder in a sachet on non-dialysis days. Levels of interleukin (IL)-6, high-sensitive C-reactive protein, thiobarbituric acid reactive substances plasma (TBARS), protein carbonylation, indoxyl sulfate (IS) and p-cresyl sulfate were measured. Anthropometric and biochemical parameters, as well as, food intake were also evaluated. As expected, resistant starch group increased fiber intake (p > 0.01), in addition the prebiotic supplementation reduced IL-6 (p = 0.01), TBARS (p > 0.01), and IS (p > 0.01) plasma levels. No significant differences were evident in the placebo group. Prebiotic-resistant starch supplementation seems to be a promising nutritional strategy to improve inflammation, oxidative stress and to reduce IS plasma levels in CKD patients on HD.
Assuntos
Cresóis/urina , Indicã/urina , Estresse Oxidativo/efeitos dos fármacos , Prebióticos/administração & dosagem , Insuficiência Renal Crônica/dietoterapia , Amido/metabolismo , Ésteres do Ácido Sulfúrico/urina , Adulto , Antropometria , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/urina , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Urina/química , Zea mays/química , Zea mays/metabolismoRESUMO
PURPOSE: Uremic toxins produced by gut microbiota (indoxyl sulfate-IS, p-cresyl sulfate-p-CS, and indole-3-acetic acid-IAA) accumulate in hemodialysis (HD) patients and exhibit potent inflammatory effects. However, the impact of these toxins on nuclear E2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) expression in HD patients remains poorly defined. The aim of this study was to evaluate the association between uremic toxins and Nrf2/NF-κB expression in vitro (RAW 264.7 macrophage-like cells) and in peripheral blood mononuclear cells from HD patients. METHODS: Uremic toxins, C-reactive protein (CRP), interleukin-6 (IL-6) and malondialdehyde (MDA) levels were measured in fifteen HD patients and nine healthy individuals. RAW 264.7 macrophage-like cells were incubated with IS, as a prototype of protein-bound uremic toxin. Nrf2 and NF-κB expressions were analyzed by RT-qPCR. RESULTS: HD patients presented high levels of inflammatory markers, MDA and uremic toxins. In addition, they presented high NF-κB and low Nrf2 expression. Uremic toxins were positively correlated with NF-κB expression (IS, ρ = 0.58, p < 0.003; p-CS, ρ = 0.71, p < 0.001; IAA, ρ = 0.62, p < 0.001) and negatively with Nrf2 (IS, ρ = - 0.48, p = 0.01; p-CS, ρ = - 0.46, p < 0.02). Uremic toxins also exhibited positive correlations with CRP and MDA levels. Multivariate analysis revealed that p-CS is a determinant factor of NF-κB expression. In RAW 264.7 culture, NF-κB mRNA expression was stimulated by IS, while Nrf2 was downregulated. CONCLUSIONS: Thus, uremic toxins may stimulate NF-κB mRNA and decrease Nrf2 expression in HD patients and, consequently, trigger inflammation and oxidative stress.
Assuntos
Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Insuficiência Renal Crônica , Uremia , Idoso , Animais , Técnicas de Cultura de Células , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Interleucina-6/sangue , Masculino , Malondialdeído/sangue , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Transdução de Sinais , Uremia/etiologia , Uremia/metabolismoRESUMO
PURPOSE: This study aimed to evaluate the association among the expressions of pro- and anti-inflammatory nuclear factors (nuclear factor-kappaB, NF-κB and nuclear erythroid 2-related factor 2, Nrf2) and nutritional status in HD patients. METHODS: This cross-sectional study included eighty-three HD patients. The peripheral blood mononuclear cells were isolated and processed for the evaluation of NF-κB and Nrf2 RNAm expression by quantitative real-time polymerase chain reaction. Muscle mass was estimated by creatinine index (CI) and percentage of body fat (%BF) by anthropometry. Seven-point subjective global assessment was also used to evaluate the nutritional status. RESULTS: The NF-κB expression was negatively correlated with CI (r = -0.54, p = 0.0001), serum albumin (r = -0.32, p = 0.02) and %BF (r = -0.61, p = 0.001). Multiple linear regression analysis revealed that NF-κB expression was independently associated with CI (ß: -0.8, p = 0.013) and %BF (ß: -0.42, p = 0.04). There was no correlation among Nrf2 and anthropometric and biochemical variables. CONCLUSION: The classical NF-κB activation seems to be associated with poor nutritional status in HD patients; however, the exact underlying mechanisms deserve further studies.
Assuntos
Falência Renal Crônica , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estado Nutricional , Diálise Renal , Adulto , Antropometria/métodos , Biomarcadores/sangue , Biomarcadores/metabolismo , Composição Corporal , Brasil/epidemiologia , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Inflamação/metabolismo , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Albumina Sérica/metabolismo , Transdução de Sinais , Estatística como AssuntoRESUMO
SCOPE: Previous studies showed that the supplementation with Brazil nut is effective in improving Se status, reduce oxidative stress, and inflammation in hemodialysis (HD) patients. As the nutritional compounds may promote the reduction of inflammation by activation of nuclear factor E2-related factor 2 (Nrf2), the aim of this pilot study was to evaluate the effects of Brazil nut supplementation on Nrf2 activation in HD patients. METHODS AND RESULTS: Thirteen HD patients received one Brazil nut supplementation per day for 3 months and were compared to 12 HD patients without supplementation. Peripheral blood mononuclear cells were isolated and processed for expression of nuclear factor kappa B, Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) by quantitative real-time PCR. Plasma malondialdehyde, C-reactive protein and IL-6 levels were measured before and after supplementation. The Nrf2 expression increased and nuclear factor kappa B expression reducedpost supplementation. In addition, the cytokines and malondialdehyde levels decreased significantly. No significant alterations were found in the control group. CONCLUSION: This preliminary result indicates the effectiveness of Brazil nut supplementation on human Nrf2 activation in HD patients and could be a possible explanation for the beneficial effects of this nut as a bioactive compound.
Assuntos
Bertholletia/química , Fator 2 Relacionado a NF-E2/metabolismo , Diálise Renal , Adulto , Idoso , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Projetos PilotoRESUMO
Uremic toxins are compounds normally excreted in urine that accumulate in patients with chronic kidney disease as a result of decreased renal clearance. Phenylacetic acid (PAA) has been identified as a new protein bound uremic toxin. The purpose of this study was to investigate in vitro the interaction between PAA and human serum albumin (HSA) at physiological and pathological concentrations. We used ultrafiltration to show that there is a single high-affinity binding site for PAA on HSA, with a binding constant on the order of 3.4 × 10(4) M(-1) and a maximal stoichiometry of 1.61 mol per mole. The PAA, at the concentration reported in end-stage renal patients, was 26% bound to albumin. Fluorescent probe competition experiments demonstrated that PAA did not bind to Sudlow's site I (in subdomain IIA) and only weakly bind to Sudlow's site II (in subdomain IIIA). The PAA showed no competition with other protein-bound uremic toxins such as p-cresyl-sulfate or indoxyl sulfate for binding to serum albumin. Our results provide evidence that human serum albumin can act as carrier protein for phenylacetic acid.
Assuntos
Fenilacetatos/química , Albumina Sérica/química , Linhagem Celular , Humanos , Ligação Proteica , Domínios Proteicos , Insuficiência Renal Crônica/sangue , Albumina Sérica/metabolismoRESUMO
PURPOSE: To evaluate nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappaB (NF-κB) mRNA expression in nondialysis chronic kidney disease (CKD) patients, comparing with data from hemodialysis (HD) patients and healthy individuals. METHODS: Twenty nondialysis CKD patients (62.0 ± 8.1 years old, 11 men, estimated glomerular filtration rate of 36.8 ± 13.6 mL/min/1.73 m(2)), twenty HD patients (55.0 ± 15.2 years old, 13 men, and dialysis vintage of 76.5 ± 46.3 months) and eleven healthy individuals (50.9 ± 8.0 years old, 6 men) were enrolled in the study. The peripheral blood mononuclear cells were isolated and processed for the evaluation of expression of NF-κB and Nrf2 by quantitative real-time polymerase chain reaction. RESULTS: Nrf2 mRNA expression was significantly higher in nondialysis (1.12 ± 0.57) when compared to HD patients (0.58 ± 0.35, p = 0,006) but similar to healthy individuals (1.13 ± 0.64). Inversely, NF-κB mRNA expression was lower in nondialysis (1.21 ± 0.71) when compared to HD patients (2.08 ± 0.7, p < 0.0001) and similar to healthy individuals (1.04 ± 0.22). Nrf2 mRNA was positively correlated with NF-κB mRNA expression in nondialysis CKD patients (r = 0.52, p = 0.02) and healthy individuals (r = 0.77, p < 0.006). By contrast, Nrf2 mRNA was inversely correlated with NF-κB mRNA expression (r = -0.65, p = 0.003) in HD patients. CONCLUSION: Nondialysis CKD patients may conserve regular homeostatic balance between Nrf2 and NF-κB expressions, being comparable to healthy individuals. However, HD patients seem to have Nrf2 downregulation and NF-κB upregulation. Thus, the association among Nrf2 and NF-κB expressions and nutritional status, kidney disease progression or immune deregulation deserve further investigation.