1,720,982 research outputs found
L-Arginine and its metabolites in kidney and cardiovascular disease
No full textL-Arginine is a semi essential amino acid synthesised from glutamine, glutamate and proline via the intestinal-renal axis in humans and most mammals. L-Arginine degradation occurs via multiple pathways initiated by arginase, nitric-oxide synthase, Arg: glycine amidinotransferase, and Arg decarboxylase. These pathways produce nitric oxide, polyamines, proline, glutamate, creatine and agmatine with each having enormous biological importance. Several disease are associated to an L-arginine impaired levels and/or to its metabolites: in particular various L-arginine metabolites may participate in pathogenesis of kidney and cardiovascular disease. L-Arginine and its metabolites may constitute both a marker of pathology progression both the rationale for manipulating L-arginine metabolism as a strategy to ameliorate these disease. A large number of studies have been performed in experimental models of kidney disease with sometimes conflicting results, which underlie the complexity of Arg metabolism and our incomplete knowledge of all the mechanisms involved. Moreover several lines of evidence demonstrate the role of L-arg metabolites in cardiovascular disease and that L-arg administration role in reversing endothelial dysfunction, which is the leading cause of cardiovascular diseases, such as hypertension and atherosclerosis. This review will discuss the implication of the mains L-arginine metabolites and L-arginine-derived guanidine compounds in kidney and cardiovascular disease considering the more recent literature in the field
Indoxyl sulphate, a tryptophan metabolite, affects astrocyte response during neuroinflammation
Full text linkIndoxyl sulfate (IS) is a protein-bound uremic toxin derived from dietary tryptophan metabolism. Tryptophan is metabolized into indole by intestinal bacteria, after intestinal absorption is further converted to IS in the liver and then excreted by kidneys. In patients with impaired kidney function, such as chronic kidney disease (CKD), IS is recognized as a uremic toxin that accumulates in the blood inducing nephrotoxicity and impairing immune response. CKD is characterized by various complications such as neurological dysfunction. Since neuroinflammation has also been recognized to contribute to cognitive complications, and because CKD patients are also affected by immune dysfunction, we evaluated the effect of IS on C6 rat astroglial cell line in inflammatory conditions. IS, at uremic concentrations (60-15 pM), added for I h and then simultaneously with lipopolysaccharide from E coli (LPS; I ltgl ml) + Interferon y (IFN; 100u/ml) for 24h, significantly increased nitric oxide release in C6 cells at all tested concentrations. In the same experimental conditions, IS induced also a significant increase in inducible nitric oxide synthase and cyclooxygenase-2 expression, in tumor necrosis factor-d levels and in nitrotyrosine formation in astrocytes. Moreover, IS induced also nuclear factor-kB activation and aryl hydrocarbons receptor nuclear translocation in C6 cells in presence of LPS + IFN, thus contributing to inflammatory response modulation. In addition, wound healing assay indicated that IS caused also a reduction in astrocytes migration during inflammation. These results indicate that IS significantly affects astrocyte function increasing inflammatory response during neuroinflammation, thus potentially contributing to neurological complications observed in CKD
Astragalus membranaceus extract attenuates inflammation and oxidative stress in intestinal epithelial cells via NF-ÎoB activation and Nrf2 response
Full text linkAstragalus membranaceus, dried root extract, also known as Astragali radix, is used in traditional Chinese medicine as a tonic remedy. Moreover, it has been reported that Astragalus membranaceus could attenuate intestinal inflammation; however, the underlying mechanism for its anti-inflammatory activity in intestinal epithelial cells (IECs) remains unclear. In this study, we evaluated Astragalus membranaceus extract (5â100 Î1⁄4g/mL) in a model of inflammation and oxidative stress for IECs. We showed that Astragalus membranaceus extract reduced the inflammatory response induced by lipopolysaccharide from E. coli (LPS) plus interferon-Î3 (IFN), decreasing tumor necrosis factor-α (TNF-α) release, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, nitrotyrosine formation, nuclear factor-ÎoB (NF-ÎoB) activation, and reactive oxygen species (ROS) release in the non-tumorigenic intestinal epithelial cell line (IEC-6). The antioxidant potential of Astragalus membranaceus extract was also evaluated in a model of hydrogen peroxide (H2O2)-induced oxidative stress in IEC-6, indicating that this extract reduced ROS release and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and the expression of antioxidant cytoprotective factors in these cells. The results contributed to clarify the mechanisms involved in Astragalus membranaceus extract-reduced inflammation and highlighted the potential use of this extract as an anti-inflammatory and antioxidant remedy for intestinal diseases
Olive oil polyphenols extracts inhibit inflammatory markers in J774A.1 murine macrophages and scavenge free radicals
No full textHere we evaluate the olive oil antiradical and anti-inflammatory potential through its polyphenols extracts and examine the influence of olive maturity on olive oil quality properties, polyphenols composition and biological potentials. Samples have been obtained from minor Tunisian olive cultivars (Chemchali, Fouji and Zarrazi) at different maturity indices. Principal quality properties were evaluated and polyphenols analysis was carried out by Folin Ciocalteu reagent and HPLC-UV-MS. Antiradical activity was examined by DPPH and FRAP scavenging assays while J774A.1 murine macrophages were used to evaluate anti-inflammatory potential by analyzing NO production with Griess reagent method and iNOS and COX-2 expression by cytofluorimetric analysis. Our results revealed that quality characteristics, total phenol content, as well as phenolic compound concentrations were significantly affected by the olive maturity levels. On the other hand, the polyphenols extracts showed an interesting radical scavenging capacity and a potential ability to inhibit inflammatory markers at 90% for NO release and 75% for iNOS expression. Thus, our study establishes that olive oil through its polyphenols extracts has a substantial antiradical and anti-inflammatory potential. Likewise a lot of attention should be attributed to olive ripening level in order to decide the optimum harvesting time
Safety assessment of two antimicrobial peptides with food industry potential application: in vitro study
No full textTwo peptides, rNterC and rTM2C, including 13 and 15 aminoacids respectively, were designed from proteins which are known to bind orto be targeted to outer mitochondrial membrane. These peptides were modified to increase antimicrobial potential considering the appropriate balance among their total net charge, amphipathicity and hydrophobicity.
These peptides were able to efficiently and selectively inhibit Listeria monocytogenes (NCTC 11994-HPA - London) growth, an important foodborne pathogen. Therefore rNterC and rTM2C could be proposed in food industry to increase the shelf life of very valuable foods. In this study we assessed the toxicity of rNterC and rTM2C in a model of non-tumorigenic intestinal epithelial cells (IEC-6). Antiproliferative assay, performed at 24, 48 and 72 h, showed a weak antiproliferative effect, in particular for rNterC, however indicating an IC50>40 μM for both peptides. The intestinal epithelium when injured by various stimuli (e.g. normal digestion, toxic substances, inflammation, oxidative stress) undergoes a wound healing process. rNterC and rTM2C peptides induces a weak reduction in the restitution process both in normal and inflammatory conditions (induced by Lipopolysaccharide from E.coli plus Interferon γ) in IEC-6 with an IC50>40 μM for both peptides. Our data on IEC-6 cells indicate that rNterC and rTM2C show only a weak antiproliferative activity and a weak effect on migration rate in IEC-6. Between the two peptides the more safe seems to be rTM2C that have the best antimicrobial activity against L. monocytogenes, despite the evaluation of other parameters will be necessary to further assess its safety
Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells
No full textMycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern
Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells.
No full textMycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kappa B and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern
Muscle stimulation in elderly patients with CKD and sarcopenia
Full text linkAim of our study was to assess the potential effects of high-tone external muscle stimulation (HTEMS) on improvement of endothelial dysfunction (ED) and kidney damage in elderly patients with chronic kidney disease (CKD), sarcopenia and/or serious physical disability with a high Multidisciplinary Prognostic Index (MPI).
METHODS:
We enrolled 12 consecutive CKD patients with MPI > 0,66 from January 1st, 2008 to December 31st, 2014. Six patients underwent a 2-hours HTEMS during the first day (group A) and the other six patients (group B) underwent a sham experiment with HTEMS without power supply. After 24 hours, patients of group A were shifted to group B and viceversa. Nitrite/nitrate (NOx), endotheline-1 (ET-1) and urine creatinine concentration were measured in all patients.
RESULTS:
During HTEMS urine amount increased by 22% (p=0.049), so did urine creatinine that increased by 40%, (p=0.034) and creatinine clearance that increased by 26% (p=0.041). There was no statistical difference in urine nitrogen (that raised by 11%, p=0.526), urine sodium (that reduced by 42%, p=0.121) and urine potassium levels (p=0,491). At the same time, NOx changed from 44.15.1 to 38.45.3 M/L after 1 hour, to 36.44.8 M/L after 2 hours, to 41.15.7 M/L after 3 hours and to 46,95.0 M/L after 4 hours (p=0.008) during HTEMS, while it did not vary during the sham section of the experiment, respectively 43.66.1 M/L , 436.4 M/L, 42.85.5 M/L, 434.7 M/L, and 42.85.8 M/L (p=0.992).
CONCLUSION:
Our study showed that HTEMS may improve microcirculation and, through this mechanism, may reduce kidney damage in elderly patients with CKD and severe muscle atrophy
High-tone external muscle stimulation in patients with acute kidney injury (AKI): Beneficial effects on NO metabolism, asymmetric dimethylarginine, and endothelin-1
No full textAbstract
OBJECTIVES:
The aim of this study was to assess potential effects of hightone external muscle stimulation (HTEMS) on parameters of endothelial dysfunction (ED) in patients with acute kidney injury (AKI).
BACKGROUND:
The bad outcome of AKI patients is markedly influenced by ED, microinflammation, oxidative stress and protein hypercatabolism. Recently, we have shown that intradialytic application of HTMS was associated with a faster resolution of AKI. Here, we investigated in the same cohort of patients whether parameters of ED such as nitric oxide (NO), asymmetric-dimethylarginine (ADMA), and endothelin 1 (ET-1) are modulated by HTEMS as compared to non-HTEMS-treated AKI patients.
METHODS:
In a post-hoc study we analyzed plasma samples of the 34 AKI patients stage 5, of whom 17 underwent intradialytic HTEMS treatment while the other 17 served as AKI dialysis controls. Measurements included plasma nitrate and nitrite (NOx), ADMA, ET-1 and were performed before and on days 3, 7, 14, 21, and 28 after start of daily dialysis. Additional 16 healthy volunteers served as controls.
RESULTS:
Initially, in both AKI groups NOx levels were markedly lower and ADMA and ET-1 levels were higher compared to the healthy controls. After initiation of daily hemodialysis the HTEMS group showed a faster improvement of NOx and ET-1 (after 1 week) and ADMA levels (after 2 weeks) compared to the No- HTEMS group. After 2 weeks, all parameters of the HTEMS group were not different from healthy controls, while the No-HTEMSAKI group needed 3 â 4 weeks.
CONCLUSION:
Our findings suggest for the first time that in AKI patients, application of HTEMS is associated with a faster normalization of lowered NOx and elevated ADMA and ET-1 plasma levels. We hypothesize that the more rapid amelioration of these parameters in the HTEMS group contributed to the accelerated recovery of AKI. With regard to the small study groups with different causes of AKI, investigations in a greater number of AKI patients is required
Potential antioxidant peptides released after simulated gastro-intestinal digestion of Stracchino soft cheese
Full text linkAs life expectation increases, age-related pathologies become more frequent, and thus the search for new compounds, with natural origin, possessing antioxidant and anti-inflammatory is expanding. Numerous evidences have demonstrated that milk proteins are a source of bioactive encrypted peptides. In order to exert their activity, these peptides should survive during digestion; we carried out an in vitro mnltistep gastro-intestinal digestion of Stracchino soft cheese. Considering the importance of oxidative stress conditions in many diseases, the obtained peptides were fractionated by preparative liquid chromatography and subsequently evaluated thet antioxidant potential. The effect of each fraction (250-10 pglml) was evaluated in inflammatory and oxidative shess conditions in intestinal epithelial cells (IEC-6). The fractions added to IEC-ó cells. I h before and simultaneously to pro-inflammatory stimulus (Lipopolysaccharide from E coli l0 ltglml{tr Interferon f l0 U/ml) for 24 h, significantly inhibited the release of reactive oxygen species (ROS), evaluated by flow cytometry. Among tested fractions, during inflammatory conditions, fraction number two exerted the highest effect in inhibiting ROS release in IEC-6. Fraction number two showed the highest antioxidant potential also when cells were treated with hydrogen peroxide (l mM) as pro-oxidant agent. Nrf2 is an important regulator of cellular resistance to oxidants and, among tested fractions, fraction number two showed the stronger effect in activating Nrfl2. Antiproliferative assay, evaluated by MTT test, indicated that the tested fractions did not affect IEC-6 proliferation. Peptide sequences of fraction two were determined by LC-MS/MS, identified peptides belong to beta casein, in particular most intense peak possessed sequence EAMAPK
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