Malnutrition is common in haemodialysis patients and closely related to morbidity and mortality. We evaluated the effect of twelve weeks of supplementation with resveratrol and curcumin on recovery ...of bone and muscle mass and protein oxidation, lipid peroxidation on patients with chronic kidney disease and iron overload undergoing hemodialysis, we performed a randomized, double-blind, placebo-controlled trial.
We included a total of 40 patients, were randomly assigned to two groups, 20 to the group with antioxidant supplementation (Resveratrol + Curcumin) (Group A), treated with a daily oral dose of 500 mg of Resveratrol and 500 mg of Curcumin, and 20 to the control group treated with placebo (Group B).
Significant differences were found in the body composition of the patients between both groups. There was a significant difference in Body Mass Index (BMI) values (p = 0.002), fat percentage (p = 0.007), muscle mass (p = 0.01) bone mass (p = 0.01), as well as in the score of the subjective global evaluation (p = 0.03). Also differences were found between the basal and final serum levels of Triglycerides (TG) (p = 0.01), VLDL (p = 0.003). A significant decrease in the levels of serum ferritin (2003.69 ± 518.73 vs 1795.65 ± 519.00 ng/mL; p = 0.04). Nor were significant differences observed between the baseline and the final Thiobarbituric Acid Reactive Substances (TBARS) values (70.45 ± 69.21 vs 50.19 ± 32.62, p = 0.24). The same results was obtained for carbonyl values (2.67 ± 0.75 vs 2.50 ± 0.85; p = 0.50).
The present study is the first assay on patients with chronic kidney disease and iron overload that demonstrates the beneficial effects of combined supplementation with Curcumin and Resveratrol on muscle and bone mass. There was a significant decrease in circulating levels of ferritin, to finding that remarkably novel.
Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic ...disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.
Poor dietary habits such as overconsumption of hypercaloric diets characterized by a high content of fructose and fat are related to metabolic abnormalities development such as obesity, diabetes, and ...dyslipidemia. Accumulating evidence supports the hypothesis that if energy intake gradually exceeds the body's ability to store fat in adipose tissue, the prolonged metabolic imbalance of circulating lipids from endogenous and exogenous sources leads to ectopic fat distribution in the peripheral organs, especially in the heart, liver, and kidney. The kidney is easily affected by dyslipidemia, which induces lipid accumulation and reflects an imbalance between fatty acid supply and fatty acid utilization. This derives from tissue lipotoxicity, oxidative stress, fibrosis, and inflammation, resulting in structural and functional changes that lead to glomerular and tubule-interstitial damage. Some authors indicate that a lipid-lowering pharmacological approach combined with a substantial lifestyle change should be considered to treat chronic kidney disease (CKD). Also, the new therapeutic target identification and the development of new drugs targeting metabolic pathways involved with kidney lipotoxicity could constitute an additional alternative to combat the complex mechanisms involved in impaired kidney function. In this review article, we first provide the pathophysiological evidence regarding the impact of hypercaloric diets, such as high-fat diets and high-fructose diets, on the development of metabolic disorders associated with impaired renal function and the molecular mechanisms underlying tissue lipid deposition. In addition, we present the current progress regarding translational strategies to prevent and/or treat kidney injury related to the consumption of hypercaloric diets.
It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of ...neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats.
The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats.
HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.
Mucormycosis is a lethal and difficult-to-treat fungal infection caused by fungi of the order Mucorales.
Mucor lusitanicus,
a member of Mucorales, is commonly used as a model to understand disease ...pathogenesis. However, transcriptional control of hyphal growth and virulence in Mucorales is poorly understood. This study aimed to investigate the role of Tec proteins, which belong to the TEA/ATTS transcription factor family, in the hyphal development and virulence of
M. lusitanicus
. Unlike in the genome of Ascomycetes and Basidiomycetes, which have a single Tec homologue, in the genome of Mucorales, two Tec homologues, Tec1 and Tec2, were found, except in that of
Phycomyces blakesleeanus
, with only one Tec homologue.
tec1
and
tec2
overexpression in
M. lusitanicus
increased mycelial growth, mitochondrial content and activity, expression of the rhizoferrin synthetase-encoding gene
rfs
, and virulence in nematodes and wax moth larvae but decreased cAMP levels and protein kinase A (PKA) activity. Furthermore,
tec1
- and
tec2
-overexpressing strains required adequate mitochondrial metabolism to promote the virulent phenotype. The heterotrimeric G beta subunit 1-encoding gene deletant strain (Δ
gpb1
) increased cAMP-PKA activity, downregulation of both
tec
genes, decreased both virulence and hyphal development, but
tec1
and
tec2
overexpression restored these defects. Overexpression of allele-mutated variants of Tec1(S332A) and Tec2(S168A) in the putative phosphorylation sites for PKA increased both virulence and hyphal growth of Δ
gpb1
. These findings suggest that Tec homologues promote mycelial development and virulence by enhancing mitochondrial metabolism and rhizoferrin accumulation, providing new information for the rational control of the virulent phenotype of
M. lusitanicus
.
Increased fructose consumption has been associated with the development of metabolic diseases due to the modification in protein expression, altering metabolic and signaling pathways. Curcumin is a ...natural compound with a regulatory effect on genes and metabolic pathways. To identify the fructose-induced protein expression changes and the effect of curcumin on the change of protein expression in the liver of mice fed a standard diet and a high fructose diet, to elucidate the global role of curcumin. Four groups (n = 4/group) of male mice (C57BL6J) of six-weeks-old were formed. One group received a standard diet (C); another received curcumin at 0.75% w/w in the feed (C + C); one more received 30% w/v fructose in drinking water (F); and one group received 30% w/v fructose in drinking water and 0.75% w/w curcumin in food (F + C); for 15 weeks. Proteomic analysis was performed by LC-MS/MS, using the label-free technique with the MaxQuant programs for identification and Perseus for expression change analysis. Differentially expressed proteins (fold change ≥1.5 and p < 0.5) were analyzed by gene ontology and KEGG. A total of 1047 proteins were identified, of which 113 changed their expression in mice fed fructose, compared to the control group, and curcumin modified the expression of 64 proteins in mice fed fructose and curcumin compared to mice that only received fructose. Curcumin prevented the change of expression of 13 proteins involved in oxidative phosphorylation (NDUFB8, NDUFB3, and ATP5L) in the cellular response to stress (PSMA5, HIST1H1D) and lipid metabolism (THRSP, DGAT1, ECI1, and ACOT13). Curcumin in mice fed the standard diet increased the expression of proteins related to oxidative phosphorylation, ribosomes, and PPAR pathways. In addition to fructose, increased expression of proteins involved in oxidative phosphorylation, ribosomes, lipid metabolism, and carbon metabolism. However, curcumin prevented expression change in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response, and lipid metabolism.
Curcumin is a natural compound with a regulatory effect on proteins and metabolic pathways. So, curcumin prevents the change of expression in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response and lipid metabolism, as a supplement with protector activity on fructose-induced toxic effects.
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•In the curcumin-treated mice, of 129 proteins that changed, two were decreased and 127 increased.•Fructose increased the expression of 104 proteins in mice liver.•38 proteins decreased and 26 increased in mice fed fructose+curcumin compared to those that only received fructose.
Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen ...consumption, nitric oxide (NO) synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice.
Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS) levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice.
These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.
Type 2 diabetes mellitus (T2DM) is characterized by chronic inflammation, in which different types of immune cells participate, such as TH17 cells and Treg cells. The aim of this study was to ...determine the relationship between Treg and Th17 in patients with different times of T2DM progression.
Nineteen control subjects and 40 patients with T2DM were included. T2DM patients were classified into two groups: the first group consisted of twenty patients with less than10 years of disease progression (T2DM < 10), and the second group included 20 patients with a disease progression of 10 years or more (T2DM ≥ 10). Additionally, an analysis was performed according to the metabolic control, depending on HbA1c levels. The peripheral blood ratio of both Th17 and Treg cells was measured by standard flow cytometry protocols.
No significant difference was found in Th17 cells of patients with T2DM < 10 or T2DM ≥ 10 and controls. With respect to CD4+CD25+FoxP3+ and CD4+CD25h Treg cells, a significant decrease was observed in patients with T2DM ≥ 10, mainly in patients with poor or moderate metabolic control. Statistical analysis performed in all patients with T2DM revealed a decrease in three cell subsets as well a negative correlation between Th17 cells and total cholesterol, CD4+CD25h cells with glucose and HbA1c levels, while a positive correlation was observed between CD4+CD25h cells and BMI.
A decrease on both Treg and Th17 cell subsets in T2DM patients was observed suggesting that the metabolic decontrol and the progression time of T2DM could modify the proportions of Th17 and Treg cells.
Obesity is currently a public health problem worldwide. Recently, non-reducing carbohydrates, that include β(2→1) and β(2→6) linkages in their structure, have been of particular interest in the field ...of obesity because they are involved in lipid metabolism. Some of these are agave fructans (AF) and oligofructose (OF). In this study, we evaluated both AF and OF on oxidative stress (OS) markers in the brain of overweight mice (OM). AF and OF decreased TBARS levels and carbonyls at different levels in hippocampus (HP), frontal cortex (FC) and cerebellum (CB) of OM. The results indicated that fructans may have anti-oxidative potential and can be used as an alternative treatment for the prevention of the consequences of this pathology.
The purpose of this study was to determine the mitochondrial content, and the oxidative and nitrosative stress of the placenta in women with gestational diabetes mellitus (GDM).
Full-term placentas ...from GDM and healthy pregnancies were collected following informed consent. The lipid peroxidation (TBARS) and oxidized protein (carbonyls) levels were determined by spectrophotometry, and 3-nitrotyrosine (3-NT), subunit IV of cytochrome oxidase (COX4), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and actin were determined by western blot, whereas ATPase activity was performed by determining the adenosine triphosphate (ATP) consumption using a High-performance liquid chromatography (HPLC) system.
TBARS and carbonyls levels were lower in the placentas of women with GDM compared with the normal placentas (p < 0.001 and p < 0.05, respectively). Also, 3-NT/actin and AMPK/actin ratios were higher in GDM placentas than in the normal placentas (p = 0.03 and p = 0.012, respectively). Whereas COX4/actin ratio and ATPase activity were similar between GDM placentas and those controls.
These data suggest that placentas with GDM are more protected against oxidative damage, but are more susceptible to nitrosative damage as compared to normal placentas. Moreover, the increased expression levels of AMPK in GDM placentas suggest that AMPK might have a role in maintaining the mitochondrial biogenesis at normal levels.
HGRL28072011 . Registered 28 July 2011.
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