Search results for "XANTHINE OXIDASE"
showing 10 items of 79 documents
Reductive and oxidative metabolism of nitrofurantoin in rat liver.
1980
The elimination of nitrofurantoin was studied in the isolated rat liver using a recirculating hemoglobin-free perfusion system. The most rapid clearance of nitrofurantoin (0.1 mM) was found under hypoxia (8 ml/min) or anoxia (11 ml/min) indicating a fast and oxygen-sensitive reductive metabolism. The hepatic elimination of nitrofurantoin under anaerobic conditions apparently is not catalyzed by xanthine oxidase, aldehyde oxidase or cytochrome P-450 as judged from the lack of influence of the inhibitors (0.1 mM) allopurinol, menadione, metyrapone, α-naphthoflavone or of carbon monoxide (50%; v/v). Under aerobic conditions the hepatic clearance of nitrofurantoin is rather low (1 ml/min) indic…
Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol
2011
Item does not contain fulltext Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-alpha production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-alpha is responsible for glutathione depletion in acute pancreatitis; and (…
Xanthine oxidase-induced oxidative stress causes activation of NF-κB and inflammation in the liver of type I diabetic rats
2009
We previously showed that xanthine oxidase activity increases in type I diabetic animals and that this is a significant cause of the oxidative stress which occurs in the disease. The aim of this work was to search for molecular links between xanthine oxidase-induced oxidative stress and inflammation in Type I diabetes and to assess the ability of allopurinol, a drug widely used in clinical practice, to prevent both processes. 3-month-old male Wistar rats were made diabetic by injection (i.p.) of either streptozotocin or alloxan. Allopurinol (32 mg/Kg) was administered (i.p) to diabetic rats after they had shown clear signs of diabetes such as glucosuria and polyuria. Hepatic phospho-IKKbeta…
Inhibition of Xanthine Oxidase by Phenolic Conjugates of Methylated Quinic Acid
2003
The caffeoyl conjugates of prenylhydroquinone glucoside and of quinic acid, either in the carboxyl-free or carboxymethyl forms, isolated from Phagnalon rupestre (Asteraceae), showed inhibitory activity on lipid peroxidation induced by Fe 2+/ascorbate and by CCl4/NADPH in rat liver microsomes, with IC50 values ranging from 3 to 11 microM. After having demonstrated their effect on the xanthine oxidase-regulated superoxide production, the active compounds were tested for the direct inhibition of this enzyme. Methylated dicaffeoylquinic conjugates competitively inhibited the enzyme and the highest potency was obtained for the 4,5-diester, with an IC50 value of 3.6 microM, nearly ten times lower…
Antioxidant activity of anti-inflammatory plant extracts
2002
The antioxidant properties of twenty medical herbs used in the traditional Mediterranean and Chinese medicine were studied. Extracts from Forsythia suspensa, Helichrysum italicum, Scrophularia auriculata, Inula viscosa, Coptis chinensis, Poria cocos and Scutellaria baicalensis had previously shown anti-inflammatory activity in different experimental models. Using free radical-generating systems H. italicum. I. viscosa and F. suspensa protected against enzymatic and non-enzymatic lipid peroxidation in model membranes and also showed scavenging property on the superoxide radical. All extracts were assayed at a concentration of 100 microg/ml. Most of the extracts were weak scavengers of the hy…
Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease
1999
In the present study, we hypothesized that exhaustive exercise in patients with chronic obstructive pulmonary disease (COPD) results in glutathione oxidation and lipid peroxidation and that xanthine oxidase (XO) contributes to free radical generation during exercise. COPD patients performed incremental cycle ergometry until exhaustion with (n = 8) or without (n = 8) prior treatment with allopurinol, an XO inhibitor. Reduced (GSH) and oxidized glutathione (GSSG) and lipid peroxides [malondialdehyde (MDA)] were measured in arterial blood. In nontreated COPD patients, maximal exercise (approximately 75 W) resulted in a significant increase in the GSSG-to-GSH ratio (4. 6 +/- 0.9% at rest vs. 9.…
Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation
2009
Skeletal muscle contractions increase superoxide anion in skeletal muscle extracellular space. We tested the hypotheses that 1) after an isometric contraction protocol, xanthine oxidase (XO) activity is a source of superoxide anion in the extracellular space of skeletal muscle and 2) the increase in XO-derived extracellular superoxide anion during contractions affects skeletal muscle contractile function. Superoxide anion was monitored in the extracellular space of mouse gastrocnemius muscles by following the reduction of cytochrome c in muscle microdialysates. A 15-min protocol of nondamaging isometric contractions increased the reduction of cytochrome c in microdialysates, indicating an …
Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator…
2010
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator…
Differential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4.
2004
The nox2-dependent NADPH oxidase was shown to be a major superoxide source in vascular disease, including diabetes. Smooth muscle cells of large arteries lack the phagocytic gp91phox subunit of the enzyme; however, two homologues have been identified in these cells, nox1 and nox4. It remained to be established whether also increases in protein levels of the nonphagocytic NADPH oxidase contribute to increased superoxide formation in diabetic vessels. To investigate changes in the expression of these homologues, we measured their expression in aortic vessels of type I diabetic rats. Eight weeks after streptozotocin treatment, we found a doubling in nox1 protein expression, while the expressio…
Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications
2015
Abstract Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin–angiotensin–aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations, ROS modulate important physiological functions through changes in cellular signalling and gene expression, overproduction of ROS may adversely alter cardiac mechanics, leading to further worsening of systolic and diastolic function. In addition, vascular endothelial dysfunction due to uncoupling of the nitric oxide synthase, activation of vascular and phagocytic membrane oxidases or mit…