Search results for "REACTIVE OXYGEN SPECIES"
showing 10 items of 879 documents
Effects of cerivastatin on adrenergic pathways, hypertrophic growth and TGFbeta expression in adult ventricular cardiomyocytes.
2010
Abstract The effects of statin treatment in the setting of heart failure have already been shown. Nevertheless, there is little knowledge about its influence on adrenergic pathways in cardiomyocytes. Therefore, this study investigated the impact of cerivastatin on adrenoceptor-mediated signalling pathways in isolated adult ventricular cardiomyocytes. It focused on two endpoints: hypertrophic growth and TGFbeta expression. Cultured cardiomyocytes were used to study rac activation (analysed by its translocation into the membrane fraction), ROS formation (H 2 DCF fluorescence) and hypertrophic growth ( 14 C-phenylalanine incorporation). Alpha- and beta-adrenoceptor stimulation showed significa…
Imeglimin Normalizes Glucose Tolerance and Insulin Sensitivity and Improves Mitochondrial Function in Liver of a High-Fat, High-Sucrose Diet Mice Mod…
2015
International audience; Imeglimin is the first in a new class of oral glucose-lowering agents currently in phase 2b development. Although imeglimin improves insulin sensitivity in humans, the molecular mechanisms are unknown. This study used a model of 16-week high-fat, high-sucrose diet (HFHSD) mice to characterize its antidiabetic effects. Six-week imeglimin treatment significantly decreased glycemia, restored normal glucose tolerance, and improved insulin sensitivity without modifying organs, body weights, and food intake. This was associated with an increase in insulin-stimulated protein kinase B phosphorylation in the liver and muscle. In liver mitochondria, imeglimin redirects substra…
The Oxidative Stress Concept of Nitrate Tolerance and the Antioxidant Properties of Hydralazine
2005
The hemodynamic and anti-ischemic effects of nitroglycerin (NTG) are rapidly blunted as a result of the development of nitrate tolerance. With initiation of NTG therapy, it is possible to detect neurohormonal activation and intravascular volume expansion. These so-called pseudotolerance mechanisms may compromise the vasodilatory effects of NTG. Long-term nitrate treatment also is associated with decreased vascular responsiveness caused by changes in intrinsic mechanisms of the tolerant vasculature itself. According to the oxidative stress concept, increased vascular superoxide (O 2 − ) production and an increased sensitivity to vasoconstrictors secondary to activation of protein kinase C co…
Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis.
2012
Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactiv…
Mitochondrial damage in aging and apoptosis.
2002
: Mitochondria are essential to cellular aging, and free radical production by mitochondria is increased with aging. The rate of oxidant production by mitochondria correlates inversely with maximal life span of species. In many species, females live longer than males. We report that mitochondrial oxidant production by females is significantly lower than that of males. However, mitochondria from ovariectomized females have a similar oxidant production as those of males. Thus, gender difference in life span can be explained, at least in part, by different oxidant generation by mitochondria. Administration of antioxidants, such as vitamins C and E, or a Ginkgo biloba extract, protects against …
Pregnenolone sulfate, a naturally occurring excitotoxin involved in delayed retinal cell death.
2002
The present study was designed to investigate the neurosteroid pregnenolone sulfate (PS), known for its ability to modulate NMDA receptors and interfere with acute excitotoxicity, in delayed retinal cell death. Three hours after exposure of the isolated and intact retina to a 30-min PS pulse, DNA fragmentation as assessed by genomic DNA gel electrophoresis and a modified in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method appeared concurrently with an increase in superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) levels. At 7 h, the increased amount of DNA laddering was accompanied by a higher number of TUN…
Critical limb ischaemia is characterised by an increased production of whole blood reactive oxygen species and expression of TREM-1 on neutrophils
2013
Atherosclerosis is a chronic inflammatory process involving polymorphonuclear neutrophils (PMN) and formation of reactive oxygen species (ROS). The aim of the present study was to investigate the phenotype of inflammatory cells in regard to the expression of triggering receptor expressed on myeloid cells (TREM)-1 and its soluble form (sTREM-1) as well as its relationship with oxidative stress in peripheral artery disease (PAD) patients.In total 90 patients with PAD (N = 30 intermittent claudication (IC)300 m absolute walking distance, N = 30 IC300 m absolute walking distance, N = 30 critical limb ischaemia (CLI)) and 30 control persons were included. ROS formation was measured at basal or s…
Resveratrol Reverses Endothelial Nitric-Oxide Synthase Uncoupling in Apolipoprotein E Knockout Mice
2010
A crucial cause of the decreased bioactivity of nitric oxide (NO) in cardiovascular diseases is the uncoupling of the endothelial NO synthase (eNOS) caused by the oxidative stress-mediated deficiency of the NOS cofactor tetrahydrobiopterin (BH(4)). The reversal of eNOS uncoupling might represent a novel therapeutic approach. The treatment of apolipoprotein E knockout (ApoE-KO) mice with resveratrol resulted in the up-regulation of superoxide dismutase (SOD) isoforms (SOD1-SOD3), glutathione peroxidase 1 (GPx1), and catalase and the down-regulation of NADPH oxidases NOX2 and NOX4 in the hearts of ApoE-KO mice. This was associated with reductions in superoxide, 3-nitrotyrosine, and malondiald…
Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial …
2013
OBJECTIVE Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition– and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS Waist, levels of triglycerides, proinflammatory cytokines (i…
Dexamethasone upregulates Nox1 expression in vascular smooth muscle cells.
2014
<b><i>Background/Aim:</i></b> It has been demonstrated that dexamethasone-induced hypertension can be prevented by the NADPH oxidase inhibitor apocynin. The effect of dexamethasone on NADPH oxidase, however, is unknown. The present study was conducted to investigate the effect of dexamethasone on the gene expression of Nox1, the major NADPH oxidase isoform in vascular smooth muscle cells. <b><i>Results:</i></b> Oral treatment of Wistar-Kyoto rats with dexamethasone (0.03 mg/kg/day) for 12 days led to an upregulation of Nox1 mRNA expression in the aorta. In cultured A7r5 rat aortic smooth muscle cells, dexamethasone increased Nox1 mRNA expressi…