Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and high serum cholesterol level are important risk factors for atherosclerosis and coronary heart disease. In the present study we tested the hypothesis whether high sodium intake, when given in combination with Western type high-fat diet, induces endothelial dysfunction and promotes atherosclerosis. Furthermore, the role and enzyme sources of increased oxidative stress were examined. Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) and control C57Bl/6 mice received either high-fat, normal-sodium diet (fat 18% and cholesterol 0.5%; NaCl 0.7%; w/w) or high-fat, high-sodium diet (7% NaCl w/w) for 12 weeks. Superoxide formation was assessed by lucigenin enhanced chemiluminescence, endothelial functions were examined ex vivo, and atherosclerotic lesions from the aorta were assessed by light microscopy. High-fat, high-sodium diet increased systolic blood pressure in LDLR(-/-) mice but not in C57Bl/6 mice, whereas it induced cardiac hypertrophy in both mouse strains. Dietary combination of fat and sodium induced endothelial dysfunction in LDLR(-/-) mice. Preincubation with a superoxide scavenger Tiron normalized endothelial dysfunction, whereas the hydrogen peroxide scavenger catalase did not alter endothelial function. High sodium intake induced superoxide formation in LDLR(-/-) mice on high-fat diet. Stimulation of muscarinic receptors in the endothelial cells by acetylcholine increased superoxide generation, whereas preincubation with the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester or endothelium removal reduced superoxide production. Inhibition of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by apocynin decreased vascular superoxide formation whereas the xanthine oxidase inhibitor oxypurinol did not significantly affect oxidative stress in LDLR(-/-) mice. In conclusion, the detrimental effects of dietary sodium on endothelial function and progression of atherosclerosis in LDLR(-/-) mice on high-fat diet are mediated by increased ROS formation mainly through uncoupled NOS and NADPH oxidase. The present study also underscores the importance of superoxide and endothelial NOS uncoupling in the pathogenesis of endothelial dysfunction.
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PMID:Effects of dietary sodium on reactive oxygen species formation and endothelial dysfunction in low-density lipoprotein receptor-deficient mice on high-fat diet. 1903 90

Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Hibiscus sabdariffa Linnaeus has been found to possess antioxidant effects. In this study, polyphenols extracted from Hibiscus sabdariffa L. (HPE) were used to detect anti-inflammatory effects on nitrite and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS) treated RAW264.7 cells. Sequentially, an animal model examination was performed to confirm the effects of HPE on LPS-induced hepatic inflammation. The results showed that HPE reduced 94.6% of xanthine oxidase activity in vitro, and decreased nitrite and PGE(2) secretions in LPS-induced cells. In LPS-treated rats, HPE significantly decreased the serum levels of alanine and aspartate aminotransferase. In the liver, lipid peroxidation and liver lesions decreased, and catalase activity and glutathione increased. The study also revealed that down-regulation of cyclooxygenase-2 (COX-2), p-c-Jun N-terminal kinase (p-JNK) and p-P38 might have been involved. In sum, this study found an anti-inflammatory potency of HPE both in vitro and in vivo.
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PMID:Polyphenols extracted from Hibiscus sabdariffa L. inhibited lipopolysaccharide-induced inflammation by improving antioxidative conditions and regulating cyclooxygenase-2 expression. 1920 85

Oxidative stress is a condition in which reactive oxygen species (ROS) or free radicals, namely O2*(-), H2O2, and *OH, are generated extra- or intracellularly and exert toxic effects on cells. The heart is one of the major organs affected by ROS. Recent evidence suggests that oxidative stress is a common denominator in many aspects of cardiovascular diseases. During myocardial oxidative stress, the generation of ROS is enhanced and the defense mechanisms of myocytes are altered. The sources of ROS in cardiac myocytes could be mitochondrial electron transport chain, nitric oxide synthase (NOS), NADPH oxidase, xanthine oxidase, and lipoxygenase/cyclooxygenase and the auto-oxidation of various substances, particularly catecholamines. In acute myocardial infarction (AMI), two distinct types of damage occur to the heart: ischemic injury and reperfusion injury, which lead to mitochondrial dysfunction in heart cells. During ischemia and reperfusion, ROS can be produced by both endothelial cells and circulating phagocytes. Ischemia also causes alterations in the defense mechanisms against ROS. Some proteins, including heat-shock proteins, are overexpressed in conditions of ischemia/reperfusion and can protect from cardiac injury. This article outlines the current understanding of oxidative stress and ROS generation and their role in cardiovascular diseases, including ischemic myocardial syndromes. The following aspects are covered: oxidative stress, mitochondrial dysfunction and pathophysiological mechanisms of atherosclerosis, precipitation of MI, sources of ROS in cardiac myocytes, effects of ROS in the heart, and ischemia and reperfusion injuries and their mechanisms.
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PMID:Oxidative stress and ischemic myocardial syndromes. 2003 98

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched by age, sex, body mass index, abdominal circumference, and homeostasis model assessment index. Production of free radicals was analyzed by measurement of xanthine oxidase activity in plasma, reduced and oxidized glutathione (GSH and GSSG, respectively), and malonyldialdehyde in levels CMCs. Antioxidant status was analyzed by measuring antioxidant enzyme activity as superoxide dismutase, catalase, and glutathione peroxidase. We have found that FH patients showed significantly higher xanthine oxidase and malonyldialdehyde enzyme activities, as well as increased GSSG and lower GSH values resulting in a higher GSSG/GSH ratio. These data indicate a higher free radical production in plasma and increased OS levels in CMCs from patients than from controls. No significant differences were found in superoxide dismutase, catalase, and glutathione peroxidase activities between both groups. These data show an important alteration of OS regulation in FH and the absence of antioxidant response in CMCs mediated by some of the major antioxidant enzymes.
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PMID:Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia. 1980 85

Chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions forms an integral part of the development of cardiovascular diseases (CVD), and in particular atherosclerosis. These ROS are released from different sources, such as xanthine oxidase, lipoxygenase, nicotinamide adenine dinucleotide phosphate oxidase, the uncoupling of nitric oxide synthase and, in particular, mitochondria. Endothelial dysfunction, characterized by a loss of nitric oxide (NO) bioactivity, occurs early on in the development of atherosclerosis, and determines future vascular complications. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not clear, oxidative stress seems to play an important role. In general, ROS are essential to cell function, but adequate levels of antioxidant defenses are required in order to avoid the harmful effects of excessive ROS production. Mitochondrial oxidative stress damage and dysfunction contribute to a number of cell pathologies that manifest themselves through a range of conditions. This review considers the process of atherosclerosis from a mitochondrial perspective, and assesses strategies for the targeted delivery of antioxidants to mitochondria that are currently under development. We will provide a summary of the following areas: the cellular metabolism of reactive oxygen species (ROS) and its role in pathophysiological processes such as atherosclerosis; currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases; and recent developments in mitochondrially-targeted antioxidants that concentrate on the matrix-facing surface of the inner mitochondrial membrane in order to protect against mitochondrial oxidative damage, and their therapeutic potential as a treatment for atherosclerosis.
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PMID:Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. 1990 43

Over the last two decades, it has become increasingly clear that reactive oxygen species (ROS), including free radicals are involved in cardiovascular disease. In recent years, there has been a growing interest in the clinical implications of these oxidants. The ROS are common by-products of many oxidative biochemical and physiological processes. They can be released by xanthine oxidase, NAD(P)H oxidase, lipoxygenases, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis. Various animal models of oxidative stress support that ROS have causal role in atherosclerosis and other cardiovascular diseases. They are too reactive to be tolerated in living tissue, and aerobic organisms use sophisticated defense system, both enzymatic and non-enzymatic for prevention of overload of free radicals. In a number of pathophysiological conditions, the delicate equilibrium between free-radical production and antioxidant capability can be altered in favor of the former, thus leading to oxidative stress and increased tissue injury. This review focuses on the biochemical evidences concerning involvement of ROS in several cardiovascular diseases, namely atherosclerosis, heart failure, hypertension and ischemia/reperfusion injury.
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PMID:Oxidative stress in cardiovascular disease. 2036 6

An increasing body of evidence suggests that oxidant stress is involved in the pathogenesis of many cardiovascular diseases, including hypercholesterolemia, atherosclerosis, hypertension, heart failure and diabetes. Recent studies have also provided important new insights into potential mechanisms underlying the pathogenesis of vascular disease induced by diabetes. Glycosylation of proteins and lipids, which can interfere with their normal function, activation of protein kinase C with subsequent alteration in growth factor expression, promotion of inflammation through the induction of cytokine secretion and hyperglycemia-induced oxidative stress are some of these mechanisms. It is widely accepted that hyperglycemia-induced reactive oxygen species contribute to cell and tissue dysfunction in diabetes. A variety of enzymatic and non-enzymatic sources of reactive oxygen species exist in the blood vessels. These include NADPH oxidase, mitochondrial electron transport chain, xanthine oxidase and nitric oxide synthase. The present article reviews the effects of reactive oxygen species on endothelial function in diabetes and addresses possible therapeutic interventions.
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PMID:Reactive oxygen species and endothelial function in diabetes. 2037 Dec 38

Oxidative stress in the vascular wall has intimately been implicated in the apoptosis of human umbilical vein endothelial cells (HUVECs) by lysophosphatidylcholine (LPC). However, the major type of reactive oxygen species (ROS) in this apoptotic signaling pathway remains to be clarified. In this study, we report that superoxide mediate LPC-induced caspase-3 dependent apoptosis in cultured HUVECs. The stimulation of HUVECs with LPC evoked apoptosis and ROS generation, and inhibited nitric oxide (NO) production in a dose-dependent manner. The classical caspase-3 dependent apoptosis was determined after 16 hours treatment by Western blotting using an antibody against cleaved caspase-3. The caspase-3 activation induced by LPC was prominently inhibited by antioxidants or NO donors and enhanced by NO inhibitors. Especially, LPC-induced caspase-3 activation was inhibited by superoxide dismutase (SOD) and enhanced by ammonium tetrathiomolybdate, SOD inhibitor. Additionally, xanthine/xanthine oxidase mixture increased the caspase-3 activation but catalase failed to reduce this superoxide-induced caspase-3 activation. These findings indicate that the superoxide generation caused by LPC activates the caspase-3 which results in HUVECs death. This study reveals some evidences linking superoxide with caspase-3 activation and provides a new dimension to superoxide-mediated caspase-3 activation in developing the endothelial dysfunction and atherosclerosis.
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PMID:Superoxide is a potential culprit of caspase-3 dependent endothelial cell death induced by lysophosphatidylcholine. 2081 64

Cardiac diseases are the major cause of death. Paraoxonase1 (PON1) is known as free radicals scavenger/anti-atherosclerosis, whereas xanthine oxidase (XO) is a free radicals generator. This study was undertaken to determine and compare the Paraoxonase and arylesterase activities of PON1 enzyme and activity of XO enzyme. The concentration of XO and PON1 enzymes along with lipid profile, lipid peroxides, and thiol level in plasma of cardiac patients (n=200) and healthy persons (n=200) of Lahore metropolitan, Pakistan was also determined. Anti-PON1 and anti-XO antibodies were developed, purified, and used to measure the concentration of PON1 and XO by competitive ELISA. It is observed that low paraoxonase (P=0.0073)/arylesterase activity (P=0.0038) of PON1 enzyme and its low concentration (P=0.0049) were observed in cardiac patients, whereas elevated level of XO activity (P=0.0129) and its concentration (P=0.0097) was observed in cardiac patients as compared with healthy persons. Low levels of HDL (P=0.0013), thiol (P=0.0014) and high level of cholesterol (P=0.0025), triglycerides (P=0.0018), LPO (P=0.0014), and LDL level (P=0.05) were observed in cardiac patients admitted in intensive care unit as compared with hypertensive patients and control subjects. It is concluded that overall low PON1 and high XO activities do cause imbalance of free radical system which ultimately leads to or enhance the cardiac pathological conditions.
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PMID:Immunobiochemical analysis of Paraoxonase1 (anti-oxidant), xanthine oxidase (oxidant) enzymes and lipid profile of cardiac disease patients in Lahore Metropolitan, Pakistan. 2087 71

Cardiovascular risk factors, such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking, stimulate the production of reactive oxygen species (ROS) in the vascular wall. Oxidative stress and endothelial dysfunction in the coronary and peripheral circulation have important prognostic implications for subsequent cardiovascular events. The pathophysiologic causes of oxidative stress are likely to involve changes in a number of different enzyme systems. Reactive oxygen species (ROS) are produced by various oxidase enzymes, including nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), cyclooxygenase, glucose oxidase, and lipooxygenase, and mitochondrial electron transport. Decreased NO production due to changes in the expression and activity of eNOS and increased degradation of NO, by reaction with superoxide account for the reduction in endothelium-dependent vascular relaxation. Recently, a variety of antioxidants have been extensively studied in clinical trials for the prevention and treatment of atherosclerosis. In small clinical studies both vitamins C and E may improve endothelial function in high-risk patients. However, larger interventional trials have been controversial, suggesting potential harm in certain high-risk populations. Antihypertensive and hypolipidemic medications exhibit well-documented antioxidant effects and improve endothelial function. However, the discussion of recent patents with the novel antioxidant strategies are required to clarify the role of antioxidant intervention in vascular diseases.
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PMID:Oxidative stress and endothelial function: therapeutic interventions. 2151 92


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