No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Rice bran modulates renal disease risk factors in animals submitted to high sugar-fat diet
Abstract
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)ENT#093;, insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)ENT#093;, dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)ENT#093;, 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.
ResearchGate has not been able to resolve any citations for this publication.
Metabolic syndrome (MS) represents worldwide public health issue characterized by a set of cardiovascular risk factors including obesity, diabetes, dyslipidemia, hypertension, and impaired glucose tolerance. The link between the MS and the associated diseases is represented by oxidative stress (OS) and by the intracellular redox imbalance, both caused by the persistence of chronic inflammatory conditions that characterize MS. The increase in oxidizing species formation in MS has been accepted as a major underlying mechanism for mitochondrial dysfunction, accumulation of protein and lipid oxidation products, and impairment of the antioxidant systems. These oxidative modifications are recognized as relevant OS biomarkers potentially able to (i) clarify the role of reactive oxygen and nitrogen species in the etiology of the MS, (ii) contribute to the diagnosis/evaluation of the disease’s severity, and (iii) evaluate the utility of possible therapeutic strategies based on natural antioxidants. The antioxidant therapies indeed could be able to (i) counteract systemic as well as mitochondrial-derived OS, (ii) enhance the endogenous antioxidant defenses, (iii) alleviate MS symptoms, and (iv) prevent the complications linked to MS-derived cardiovascular diseases. The focus of this review is to summarize the current knowledge about the role of OS in the development of metabolic alterations characterizing MS, with particular regard to the occurrence of OS-correlated biomarkers, as well as to the use of therapeutic strategies based on natural antioxidants.
Abstract Chronic hyperglycemia is the key point of macro- and microvascular complications associated with diabetes mellitus. Excess glucose is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease, which is currently the leading cause of dialysis in the world. The pathogenesis of the disease is complex, multifactorial and not fully elucidated; many factors and mechanisms are involved in the development, progression and clinical outcomes of the disease. Despite the disparate mechanisms involved in renal damage related to diabetes mellitus, the metabolic mechanisms involving oxidative/inflammatory pathways are widely accepted. The is clear evidence that a chronic hyperglycemic state triggers oxidative stress and inflammation mediated by altered metabolic pathways in a self-perpetuating cycle, promoting progression of cell injury and of end-stage renal disease. The present study presents an update on metabolic pathways that involve redox imbalance and inflammation induced by chronic exposure to hyperglycemia in the pathogenesis of diabetic kidney disease.
The kidney is an important organ in the maintenance of body homeostasis. Dietary compounds, reactive metabolites, obesity, and metabolic syndrome (MetS) can affect renal filtration and whole body homeostasis, increasing the risk of chronic kidney disease (CKD) development. Gamma oryzanol ( γ Oz) is a compound with antioxidant and anti-inflammatory activity that has shown a positive action in the treatment of obesity and metabolic diseases. Aim . To evaluate the effect of γ Oz to recover renal function in obese animals by high sugar-fat diet by modulation of adiponectin receptor 2/PPAR- α axis Methods . Male Wistar rats were initially randomly divided into 2 experimental groups: control and high sugar-fat diet (HSF) for 20 weeks. When proteinuria was detected, HSF animals were allocated to receive γ Oz or maintain HSF for more than 10 weeks. The following were analyzed: nutritional and biochemical parameters, systolic blood pressure, and renal function. In the kidney, the following were evaluated: inflammation, oxidative stress, and protein expression by Western blot. Results . After 10 weeks of γ Oz treatment, γ Oz was effective to improve inflammation, increase antioxidant enzyme activities, increase the protein expression of adiponectin receptor 2 and PPAR- α , and recover renal function. Conclusion . These results permit us to confirm that γ Oz is able to modulate PPAR- α expression, inflammation, and oxidative stress pathways improving obesity-induced renal disease.
Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in clinical care, CKD remains a major public health burden, affecting 10–15% of the population, and its prevalence is constantly growing. Due to its insidious nature, CKD is rarely diagnosed in early stages, and once developed, its progression is unfortunately irreversible. There are many factors that contribute to the setting of the inflammatory status in CKD, including increased production of proinflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, altered metabolism of adipose tissue, and last but not least, gut microbiota dysbiosis, an underestimated source of microinflammation. In this scenario, a huge step forward was made by the increasing progression of omics approaches, specially designed for identification of biomarkers useful for early diagnostic and follow-up. Recent omics advances could provide novel insights in deciphering the disease pathophysiology; thus, identification of circulating biomarker panels using state-of-the-art proteomic technologies could improve CKD early diagnosis, monitoring, and prognostics. This review aims to summarize the recent knowledge regarding the relationship between inflammation and CKD, highlighting the current proteomic approaches, as well as the inflammasomes and gut microbiota dysbiosis involvement in the setting of CKD, culminating with the troubling bidirectional connection between CKD and renal malignancy, raised on the background of an inflammatory condition.
Abstract Obesity has been pointed out as an important cause of kidney diseases. Due to its close association with diabetes and hypertension, excess weight and obesity are important risk factors for chronic kidney disease (CKD). Obesity influences CKD development, among other factors, because it predisposes to diabetic nephropathy, hypertensive nephrosclerosis and focal and segmental glomerulosclerosis. Excess weight and obesity are associated with hemodynamic, structural and histological renal changes, in addition to metabolic and biochemical alterations that lead to kidney disease. Adipose tissue is dynamic and it is involved in the production of "adipokines", such as leptin, adiponectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β and angiotensin-II. A series of events is triggered by obesity, including insulin resistance, glucose intolerance, dyslipidemia, atherosclerosis and hypertension. There is evidence that obesity itself can lead to kidney disease development. Further studies are required to better understand the association between obesity and kidney disease.
Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (
P
<
0.001
) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals (
P
<
0.001
). CAR ameliorated the changes in the stressed animals as compared with the control group (
P
<
0.001
). This study indicates that CAR can prevent restraint stress induced oxidative damage.
Chronic kidney disease (CKD), diabetes mellitus (DM) and cardiovascular diseases (CVD) are complex disorders of partly unknown genesis and mostly known progression factors. CVD and DM are the risk factors of CKD and are strongly intertwined since DM can lead to both CKD and/or CVD and CVD can lead to kidney disease. In recent years our knowledge of CKD, DM and CVD has been expanded and several important experimental, clinical and epidemiological associations have been reported. The tight cellular and molecular interactions between the renal, diabetic and cardiovascular systems in acute or chronic disease settings is becoming increasingly evident. However, the (patho-) physiological basis of the interactions of CKD, DM and CVD with involvement of multiple endogenous and environmental factors is highly complex and our knowledge still at its infancy. Not only single pathways and mediators of progression of these diseases have to be considered in these processes, but also the mutual interactions of these factors are essential. The recent advances in proteomics and integrative analysis technologies have allowed rapid progress in analyzing complex disorders and clearly show the opportunity for new efficient and specific therapies. More than a dozen pathways have been identified so far, including hyperactivity of the renin-angiotensinaldosterone system, osmotic sodium retention, endothelial dysfunction, dyslipidemia, RAS/RAF/ERK pathway, modification of the purinergic system, phosphatidylinositol 3-kinase (PI 3-kinase)-dependent signaling pathways, andinflammation, all leading to histomorphological alterations of the kidney and vessels of diabetic and non-diabetic patients. Since a better understanding of the common cellular and molecular mechanisms of these diseases may be a key to successful identification of new therapeutic targets, we review in this paper the current literature about cellular and molecular mechanisms of CKD.
Background/Aims
The aim of this study was to evaluate whether supplementation of high doses of cholecalciferol for two months in normotensive rats results in increased systolic arterial pressure and which are the mechanisms involved. Specifically, this study assesses the potential effect on cardiac output as well as the changes in aortic structure and functional properties.
Methods
Male Wistar rats were divided into three groups: 1) Control group (C, n = 20), with no supplementation of vitamin D, 2) VD3 (n = 19), supplemented with 3,000 IU vitamin D/kg of chow; 3) VD10 (n = 21), supplemented with 10,000 IU vitamin D/kg of chow. After two months, echocardiographic analyses, measurements of systolic arterial pressure (SAP), vascular reactivity, reactive oxygen species (ROS) generation, mechanical properties, histological analysis and metalloproteinase-2 and -9 activity were performed.
Results
SAP was higher in VD3 and VD10 than in C rats (p = 0.001). Echocardiographic variables were not different among groups. Responses to phenylephrine in endothelium-denuded aortas was higher in VD3 compared to the C group (p = 0.041). Vascular relaxation induced by acetylcholine (p = 0.023) and sodium nitroprusside (p = 0.005) was impaired in both supplemented groups compared to the C group and apocynin treatment reversed impaired vasodilation. Collagen volume fraction (<0.001) and MMP-2 activity (p = 0.025) was higher in VD10 group compared to the VD3 group. Elastin volume fraction was lower in VD10 than in C and yield point was lower in VD3 than in C.
Conclusion
Our findings support the view that vitamin D supplementation increases arterial pressure in normotensive rats and this is associated with structural and functional vascular changes, modulated by NADPH oxidase, nitric oxide, and extracellular matrix components.
Rice (Oryza sativa) is the most important staple food for a large part of the world's human population, especially in East and South Asia, the Middle East, Latin America, and the West Indies. It provides more than one fifth of the calories consumed worldwide by the human. It is the second leading cereal crop and staple food of half of the world's population. It is grown in at least 114 countries with global production of 645 million tons; share of Asian farmers is about 90% of the total produce. Rice bran, brown outer layer of rice kernel, is mainly composed of pericarp, aleurone, subaleurone layer, and germ. It contains appreciable quantities of nutrients like protein, fat, and dietary fiber. Furthermore, it contains substantial amount of minerals like K, Ca, Mg, and Fe. Presence of antioxidants like tocopherols, tocotrienols, and γ-oryzanol also brighten prospects of rice bran utilization for humans as functional ingredient to mitigate the life-threatening disorders. Moreover, in the developing countries, budding dilemma of food crisis, arising due to lower crop yields and escalating population, needs to utilize each pent of available resources. To provide enough food to all people, there is the holistic approach of using the by-products generated during food processing and preparations. Rice is being processed in well-established industry, but the major apprehension is the utilization of its by-products; rice bran (5-8%) and polishing (2-3%) that are going as waste. Rice processing or milling produces several streams of materials including milled rice, bran, and husk. In developing countries, rice bran is considered as a by-product of the milling process and commonly used in animal feed or discarded as a waste. The potential of producing rice bran at the global level is 29.3 million tons annually, whereas the share of Pakistan is worked out to be 0.5 million tons. In present paper, attempt has been made to highlight the significance of these valuable but neglected ingredients under various headings.
Kidney damage represents a frequent event in the course of hypertension, ranging from a benign to a malignant form of nephropathy depending on several factors, that is, individual susceptibility, degree of hypertension, type of etiology and underlying kidney disease. Multiple mechanisms are involved in determination of kidney glomerular, tubular and interstitial injuries in hypertension. The present review article discusses relevant contributory molecular mechanisms underpinning the promotion of hypertensive renal damage, such as the renin-angiotensin-aldosterone system (RAAS), oxidative stress, endothelial dysfunction, and genetic and epigenetic determinants. We highlighted major pathways involved in the progression of inflammation and fibrosis leading to glomerular sclerosis, tubular atrophy and interstitial fibrosis, thus providing a state of the art review of the pathogenetic background useful for a better understanding of current and future therapeutic strategies toward hypertensive nephropathy. An adequate control of high blood pressure, obtained through an appropriate therapeutic intervention, still represents the key strategy to achieve a satisfactory control of renal damage in hypertension. In this regard, we reviewed the impact of currently available antihypertensive pharmacological treatment on kidney damage, with particular regard to RAAS inhibitors. Notably, recent findings underscored the ability of the kidneys to regenerate and to repair tissue injuries through the differentiation of resident embryonic stem cells. Pharmacological modulation of the renal endogenous reparative process (that is, with angiotensin-converting enzyme inhibitors and AT1 angiotensin II receptor blockers), as well as future therapeutic strategies targeted to the renopoietic system, offers interesting perspectives for the management of hypertensive nephropathy.Journal of Human Hypertension advance online publication, 27 June 2013; doi:10.1038/jhh.2013.55.
Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) or a hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO+L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO+L, 10 mg/kg body weight (BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO+L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.
Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.
The metabolic syndrome is a complex of clinical features leading to an increased risk for cardiovascular disease and type 2 diabetes mellitus in both sexes. Visceral obesity and insulin resistance are considered the main features determining the negative cardiovascular profile in metabolic syndrome. The aim of this paper is to highlight the central role of obesity in the development of a chronic low-grade inflammatory state that leads to insulin resistance, endothelial and microvascular dysfunctions. It is thought that the starting signal of this inflammation is overfeeding and the pathway origins in all the metabolic cells; the subsequent increase in cytokine production recruits immune cells in the extracellular environment inducing an overall systemic inflammation. This paper focuses on the molecular and cellular inflammatory mechanisms studied until now.
Hypertension is both an important cause and consequence of chronic kidney disease. Evidence from numerous clinical trials has demonstrated the benefit of blood pressure control. However, it remains unclear whether available results could be extrapolated to patients with chronic kidney diseases because most studies on hypertension have excluded patients with kidney failure. In addition, chronic kidney disease encompasses a large group of clinical disorders with heterogeneous natural history and pathogenesis. In this paper, we review current evidence supporting treatment of hypertension in various forms of chronic kidney disease and highlight some of the gaps in the extant literature.
Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4.
Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS.
Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level.
Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.
Accumulation of advanced glycation end products (AGEs) on nucleotides, lipids, and peptides/proteins are an inevitable component of the aging process in all eukaryotic organisms, including humans. To date, a substantial body of evidence shows that AGEs and their functionally compromised adducts are linked to and perhaps responsible for changes seen during aging and for the development of many age-related morbidities. However, much remains to be learned about the biology of AGE formation, causal nature of these associations, and whether new interventions might be developed that will prevent or reduce the negative impact of AGEs-related damage. To facilitate achieving these latter ends, we show how invertebrate models, notably Drosophila melanogaster and Caenorhabditis elegans, can be used to explore AGE-related pathways in depth and to identify and assess drugs that will mitigate against the detrimental effects of AGE-adduct development.
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes mellitus, cardiovascular disease, and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term. The incidence of obesity-related glomerulopathy has increased 10-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.
Chronic kidney disease has become a serious public health issue. There are currently over 1.4 million patients receiving renal replacement therapy worldwide. One way to reduce the economic burden of chronic kidney disease would be early intervention. In order to achieve this, we should be able to identify individuals with increased risk of renal disease. An individual's genetic and phenotypic make-up puts him/her at risk for kidney disease. Factors such as race, gender, age, and family history are highly important. For instance, being of African-American decent, older age, low birth weight and family history of kidney disease are considered to be strong risk factors for chronic kidney disease. Moreover, smoking, obesity, hypertension, and diabetes mellitus can also lead to kidney disease. An uncontrolled diabetic and/or hypertensive patient can easily and quickly progress to an end-stage kidney disease patient. Exposure to heavy metals, excessive alcohol consumption, smoking, and the use of analgesic medications also constitute risks. Experiencing acute kidney injury, a history of cardiovascular disease, hyperlipidemia, metabolic syndrome, hepatitis C virus, HIV infection, and malignancy are further risk factors. Determination of serum creatinine levels and urinalysis in patients with chronic kidney disease risk will usually be sufficient for initial screening.
Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide and the single strongest predictor of mortality in patients with diabetes. DKD is a prototypical disease of gene and environmental interactions. Tight glucose control significantly decreases DKD incidence, indicating that hyperglycemia-induced metabolic alterations, including changes in energy utilization and mitochondrial dysfunction, play critical roles in disease initiation. Blood pressure control, especially with medications that inhibit the angiotensin system, is the only effective way to slow disease progression. While DKD is considered a microvascular complication of diabetes, growing evidence indicates that podocyte loss and epithelial dysfunction play important roles. Inflammation, cell hypertrophy, and dedifferentiation by the activation of classic pathways of regeneration further contribute to disease progression. Concerted clinical and basic research efforts will be needed to understand DKD pathogenesis and to identify novel drug targets.
The authors concisely review the main clinical issues arising in the management of the hypertensive patient with type 2 diabetes, in whom chronic kidney disease is prevalent and heralds increased cardiovascular morbidity and mortality. Special attention is paid to the clinical meaning, relevance and limits of albumin excretion and glomerular filtration rate, the two widely used markers of reduced kidney function during the course of chronic diseases like diabetes and hypertension. The main therapeutic strategies involving blood pressure and glycemic control, treatment of dyslipidemia and improvement of lifestyle are discussed from the viewpoint of a general practitioner dealing with the clinical complexity of these patients.
The multiligand receptor of the immunoglobulin superfamily, receptor for advanced glycation endproducts (RAGE), is a signal transduction receptor that binds advanced glycation endproducts, certain members of the S100/calgranulin family of proteins, high mobility group box 1 (HMGB1), advanced oxidation protein products, and amyloid (beta-sheet fibrils). Initial studies investigating the role of RAGE in renal dysfunction focused on diabetes. However, RAGE also has roles in the pathogenesis of renal disorders that are not associated with diabetes, such as obesity-related glomerulopathy, doxorubicin-induced nephropathy, hypertensive nephropathy, lupus nephritis, renal amyloidosis, and ischemic renal injuries. Experiments that have employed transgenic mouse models, pharmacological blockade of RAGE, or genetic deletion or modification of RAGE indicate that modulation of RAGE expression or function affects the functional and pathological properties of these nephropathies. Accumulating evidence links RAGE to the pathogenesis of nephropathies, indicating that antagonism of RAGE might be a strategy for the treatment of chronic kidney disease.
Chronic kidney disease is often not associated with significant symptoms or abnormalities in common laboratory test results. Diagnosis is supposedly facilitated by calculating the glomerular filtration rate (GFR) from serum creatinine. A reference range GFR, however, does not exclude renal disease, because renal disease causes the subsequent decrease of renal function. Thorough analysis of proteinuria, however, requires a profound knowledge of the renal handling of the different marker proteins of glomerular and tubular origin. This paper summarizes the scientific basis, explains the diagnostic rationale and proves the concept by analyzing 5669 samples, where GFR and proteinuria work-up were available. 63% (1446 of 2287) of the samples with a GFR above 60 showed either glomerular (37.8%, n=865) or tubular proteinuria (25.4%, n= 581). The quantity of proteinuria increased severely with decreasing kidney function. The rate of glomerular proteinuria remained nearly constant in the different GFR groups, while primarily tubular proteinuria increased from 23% to 63%. A proteinuria pattern indicating a good response to therapy was frequently combined with a high GFR (selective glomerular proteinuria/ incomplete tubular proteinuria), while the severe forms of unselective or complete tubular proteinuria associated with a severe GFR decrease. Regression analysis showed a better inverse correlation of GFR with tubular (r=-0.643) than glomerular markers (r=-0.360; combined r=-0.646). We believe that this complex interrelated laboratory information must be delivered most effectively, i.e. with the use of a knowledge based system in combination with improved, visual oriented laboratory output.
This study was conducted to determine the relative cholesterol-lowering effects of several levels of full-fat rice bran in hamsters. In addition, the separate effects of defatted rice bran and/or crude rice bran oil were investigated at levels equivalent to those present in 43.7% full-fat rice bran. Diets containing 10.9, 21.8, 32.8 or 43.7% full-fat rice bran, 35% defatted rice bran and/or 9% rice bran oil were fed to 4-wk-old male hamsters. All diets contained 10% total dietary fiber, 9% fat and 3.2% nitrogen; hypercholesterolemic diets contained 0.3% cholesterol; two diets were cholesterol-free, i.e., 10% cellulose and 43.7% full-fat rice bran. After 21 d, plasma and liver cholesterol, plasma triglycerides and liver weights were significantly greater in hamsters fed the 10% cellulose diet with 0.3% cholesterol compared with those fed the cholesterol-free cellulose diet. In animals fed cholesterol-free diets, plasma cholesterol values were significantly lower in those fed the 43.7% full-fat rice bran diet than in those fed the cellulose diet. In animals fed cholesterol-containing diets, plasma and liver cholesterol were significantly lower in animals fed the 43.7% full-fat rice bran diet than in those fed the cellulose diet. Plasma cholesterol reductions were significantly correlated to the level of rice bran in the diet. In cholesterol-fed hamsters, total liver cholesterol content was significantly lower in those fed the defatted rice bran diet with rice bran oil compared with those fed the cellulose diet. Full-fat rice bran was the only treatment that significantly lowered both plasma and liver cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.
The antioxidant activities of vitamin E (alpha-tocopherol, alpha-tocotrienol, gamma-tocopherol, and gamma-tocotrienol) and gamma-oryzanol components (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate) purified from rice bran were investigated in a cholesterol oxidation system accelerated by 2,2'-azobis(2-methylpropionamidine) dihydrochloride. All components exhibited significant antioxidant activity in the inhibition of cholesterol oxidation. The highest antioxidant activity was found for 24-methylenecycloartanyl ferulate, and all three gamma-oryzanol components had activities higher than that of any of the four vitamin E components. Because the quantity of gamma-oryzanol is up to 10 times higher than that of vitamin E in rice bran, gamma-oryzanol may be a more important antioxidant of rice bran in the reduction of cholesterol oxidation than vitamin E, which has been considered to be the major antioxidant in rice bran. The antioxidant function of these components against cholesterol oxidation may contribute to the potential hypocholesterolemic property of rice bran.
Studies in the general population suggest that low-grade inflammation, endothelial dysfunction, and platelet activation are associated with an increased risk of cardiovascular events.
Markers of inflammation, endothelial dysfunction, and platelet activation were measured in 334 patients with chronic kidney disease (serum creatinine >1.47 mg/dL [>130 micromol/L] at screening) and compared with 2 age- and sex-matched control groups, 1 comprising 92 patients with coronary artery disease and the other comprising 96 apparently healthy individuals with no history of cardiovascular or kidney disease.
There was evidence of low-grade inflammation in the chronic renal impairment group compared with healthy controls, with higher concentrations of C-reactive protein (3.70 versus 2.18 mg/L, P < 0.01) and fibrinogen (3.48 versus 2.67 g/L, P < 0.001) and lower serum albumin concentration (41.8 versus 44.0 g/dL [418 versus 440 g/L], P < 0.001). More severe renal impairment was associated with a trend towards higher fibrinogen and lower albumin concentrations (both P < 0.001), although there was no association with higher C-reactive protein level. As compared to healthy controls, plasma von Willebrand factor (142 versus 108 IU/dL, P < 0.001) and soluble P-selectin concentrations (57.0 versus 43.3 ng/mL, P < 0.001) were also higher in the chronic renal impairment group. More severe renal impairment was associated with a trend towards higher levels of von Willebrand factor (P < 0.001) and of soluble P selectin (P < 0.05).
This cross-sectional analysis demonstrates that chronic kidney disease is associated with low-grade inflammation, endothelial dysfunction, and platelet activation, even among patients with moderate renal impairment.
Data curation: Francisqueti-Ferron FV
- C R Correa
Correa CR.
Data curation: Francisqueti-Ferron FV; Garcia JL;
Formal analysis: Francisqueti-Ferron FV
- F Moreto
Moreto F. Formal analysis:
Francisqueti-Ferron FV;
Funding acquisition: Correa CR
- C R Correa
Correa CR; Funding acquisition:
Correa CR. Methodology: Francisqueti-Ferron FV;
Project administration: Francisqueti-Ferron FV
- J S Siqueira
Siqueira JS.
Project administration: Francisqueti-Ferron FV;
Writing original draft: Francisqueti-Ferron FV
- C R Correa
Correa CR. Writing original draft: Francisqueti-Ferron FV;
Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease
- V Cachofeiro
- M Goicochea
- S G Vinuesa
- P Oubĩa
- V Lahera
- J Lũo
Cachofeiro V, Goicochea M, Vinuesa SG, Oubĩa P, Lahera V, Lũo
J. Oxidative stress and inflammation, a link between chronic kidney
disease and cardiovascular disease. Kidney Int. 2008 Dec;74(Suppl
111):S4-S9. DOI: https://doi.org/10.1038/ki.2008.516
Effect of gamma-oryzanol as therapeutic agent to prevent cardiorenal metabolic syndrome in animals submitted to high sugar-fat diet
- F V Francisqueti
- I O Minatel
- Ajt Ferron
- Sgz Bazan
- V S Silva
- J L Garcia
Francisqueti FV, Minatel IO, Ferron AJT, Bazan SGZ, Silva VS,
Garcia JL, et al. Effect of gamma-oryzanol as therapeutic agent
to prevent cardiorenal metabolic syndrome in animals submitted to high sugar-fat diet. Nutrients. 2017 Dec;9(12):1299.
Guide to the care and use of experimental animals. Ottawa: Canadian Council on Animal Care (CCAC)
- E D Olfert
- B M Cross
- A A Mcwilliam
Olfert ED, Cross BM, McWilliam AA. Guide to the care and
use of experimental animals. Ottawa: Canadian Council on
Animal Care (CCAC); 1993. v. 1.
Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study
GBD Chronic Kidney Disease Collaboration. Global, regional,
and national burden of chronic kidney disease, 1990-2017:
a systematic analysis for the Global Burden of Disease Study
2017. Lancet. 2020 Feb;395(10225):709-33.
Rice bran reduces weight gain and modulates lipid metabolism in rats with high-energy-diet-induced obesity
- S C Yang
- W C Huang
- X E Ng
- M C Lee
- Y J Hsu
- C C Huang
Yang SC, Huang WC, Ng XE, Lee MC, Hsu YJ, Huang CC, et
al. Rice bran reduces weight gain and modulates lipid metabolism in rats with high-energy-diet-induced obesity. Nutrients.
2019 Sep;11(9):2033.