Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal and human studies have shown that carvedilol has significant antioxidant properties compared with other beta-blockers. The objective of this study was to determine if these antioxidant effects are detectable in patients with heart failure and to compare carvedilol with the selective beta-blocker metoprolol. Twenty-four patients with chronic heart failure were randomly assigned to receive either carvedilol or metoprolol in a double-blind control trial for 12 weeks in a University teaching hospital clinic. Blood pressure, heart rate, exercise tolerance, left ventricular ejection fraction, plasma total antioxidant status, erythrocyte superoxide dismutase, and glutathione peroxidase activities were determined at baseline and every 4 weeks up to 12 weeks. The results showed that erythrocyte superoxide dismutase and glutathione peroxidase were significantly reduced in carvedilol treated patients after 12 weeks of therapy, whereas metoprolol had no significant effect, although the clinical improvement over the short-term was similar with both drugs. Thus carvedilol, in addition to improving symptoms in heart failure, also possesses significant antioxidant properties. Whether this additional action influences long-term outcome is at present unknown.
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PMID:Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial. 1115 73

Many clinical and experimental studies have established the beneficial effect of kinins in hypertension, heart failure and ischaemia-reperfusion syndrome, but little attention has been given to the role of kinins in hyperglycaemic conditions. The purpose of the present study was to determine the influence of bradykinin on the levels of glucose, insulin, malondialdehyde and hydrogen peroxide, as well as antioxidative enzyme activity in rats with streptozotocin (STZ)-induced acute hyperglycaemia. In STZ-induced hyperglycaemic rats the levels of glucose, hydrogen peroxide and malondialdehyde were increased by 256% (from 6.0+/-0.3 to 21.4+/-1.3 mmol/l, P<0.001), 33% (from 1.9+/-0.1 to 5.6+/-0.3 mmol H(2)O(2)/ml, P<0.001) and 19% (from 3.7+/-0.3 to 4.9+/-0.2 nmol/l, P<0.001) respectively. The activity of superoxide dismutase, catalase and glutathione peroxidase and the level of insulin were decreased by 46% (from 1367+/-73 to 737+/-59 U/g Hb, P<0.001), 36% (from 2.3+/-0.3 to 1.4+/-0.1 U Bergmayera/g Hb, P<0.001), 31% (from 236+/-19 to 163+/-24 U/g Hb, P<0.001) and 91% (from 47.5+/-1.7 to 2.4+/-0.5 mU/l, P<0.001) respectively in rats treated with streptozotocin. The administration of bradykinin caused the decrease in glucose, hydrogen peroxide and malondi-aldehyde levels by 38% (from 21.4+/-1.3 to 13.3+/-1.0 mmol/l, P<0.001), 37% (from 5.6+/-0.3 to 4.3+/-0.2 mmol H2O2/ml, P<0.001), 39% (from 4.9+/-0.2 to 3.0+/-0.2 nmol/l, P<0.001) respectively and the increase in insulin level and superoxide dismutase, catalase and glutathione peroxidase activity by 62% (from 2.4+/-0.5 to 4.0+/-0.4 mU/l, P<0.001), 23% (from 736.8+/-58.5 to 906.7+/-47.8 U/g Hb, P<0.001), 23% (from 1.4+/-0.1 to 1.9+/-0.1 U Bergmayera/g Hb, P<0.01) and 19% (from 163.1+/-23.6 to 202.3+/-11.7 U/g Hb, P<0.001) respectively in rats with hyperglycaemia. Thus, bradykinin is able to reduce oxidative stress in hyperglycaemic conditions.
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PMID:The effect of bradykinin on the oxidative state of rats with acute hyperglycaemia. 1116 87

Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.
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PMID:Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model. 1123 11

Heart failure due to chronic iron overload is a leading cause of cardiovascular mortality in the second and third decades of life worldwide, but its mechanism is not known. Deficiencies of selenium have been shown to result in damage to the myocardium and to the development of various cardiomyopathies. In the current investigation, the dose-dependent effects of chronic iron toxicosis on heart tissue concentrations of selenium and the protective antioxidant enzyme glutathione peroxidase (GPx) were investigated in a murine model of iron-overload cardiomyopathy (n = 20). Significant dose-dependent decreases in heart tissue selenium concentrations (r = -0.95, p < 0.001) and selenium-dependent GPx activity (r = -0.93, p < 0.001) were observed in chronically iron-loaded mice in comparison with placebo controls. These results suggest that dietary supplementation with selenium may be beneficial in the clinical management of disorders of iron metabolism.
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PMID:Decreasing effects of iron toxicosis on selenium and glutathione peroxidase activity. 1185 44

Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.
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PMID:Early changes in myocardial antioxidant enzymes in rats treated with adriamycin. 1203 Mar 76

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
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PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

We studied the role of oxidative stress in the pathogenesis of primary pulmonary hypertension. In patients with primary pulmonary hypertension the content of malonic dialdehyde in the plasma was higher than in healthy volunteers (5.18 0.46 and 2.95 0.14 nmol/liter, respectively, p<0.01). However, glutathione peroxidase activity in the plasma decreased in these patients (0.50 0.17 vs. 1.19 0.14 U/ml in the control, p<0.05). By contrast, glutathione peroxidase activity in erythrocytes from patients surpassed the control (6.13 0.39 and 4.63 0.45 U/h hemoglobin). The increase in malonic dialdehyde content in the plasma and glutathione peroxidase activity in erythrocytes and the decrease in glutathione peroxidase activity in the plasma were most pronounced in patients with severe cardiac insufficiency and pulmonary hypertension. Our results indicate that antioxidant preparations improve the prognosis in patients with primary pulmonary hypertension.
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PMID:Oxidative stress in patients with primary pulmonary hypertension. 1244 71

Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.
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PMID:Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. 1282 51

In the left ventricle subjected to pressure overload activity, the antioxidant enzymes increased at the hyperfunctional stage. During the transition to heart failure, these enzymes are down-regulated, oxidative stress increases, and apoptosis progresses. Maladaptative activation of the antioxidant enzymes at an early stage may contribute to the intrinsic vulnerability of right ventricle to pressure overload. The authors studied changes in expression and activity of the enzymes manganese and copper-zinc superoxide dismutases, glutathione peroxidase, and catalase in the right ventricle of rat following induction of pulmonary hypertension by injection of monocrotaline. Increase in the manganese superoxide dismutase was delayed to the late failing stage, activity of glutathione peroxidase was depressed throughout, and only catalase was activated at the early stage before returning to control levels. This inability to activate antioxidant enzymes may contribute to the deleterious consequences of pressure overload on right ventricle systolic function.
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PMID:The activation pattern of the antioxidant enzymes in the right ventricle of rat in response to pressure overload is of heart failure type. 1450 27

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.
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PMID:Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction. 1457 98


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