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)

Cirrhosis is associated with altered gastrointestinal function, and bacterial translocation from the gut plays an important role in the etiology of spontaneous bacterial peritonitis (SBP) seen in this condition. Although alterations in gut motility and intestinal permeability are recognized in cirrhosis, the intestinal damage at the cellular and subcellular levels is not well understood. This study looked at the mucosal alterations in experimental cirrhosis and the role of oxygen free radicals in this process. It was shown that cirrhosis results in oxidative stress in the intestine, as seen by increased xanthine oxidase (XO) activity and altered antioxidant status. Cirrhosis also affects enterocyte mitochondrial function, as assessed by respiratory control ratio, swelling, and calcium flux. Increased lipid peroxidation of the brush border membranes (BBMs) was seen along with altered intestinal transport. In conclusion, this study shows that intestinal mucosal alterations are seen in experimental cirrhosis and are possibly mediated by oxidative stress.
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PMID:Intestinal mucosal alterations in experimental cirrhosis in the rat: role of oxygen free radicals. 1187 Mar 76

Chronic gut inflammation is associated with radical oxygen species (ROS) genesis. ROS may activate certain transcription factors such as nuclear factor kappa beta (NF-kappaB), which regulates cyclooxygenase-2 (COX-2). Diquat, a food contaminant, is responsible for oxidative stress. This work aimed to establish the involvement of ROS and prostanoids on diquat-induced gastrointestinal inflammation and mast cell hyperplasia. Diquat increased gastrointestinal MPO activity and mast cell number. Its effect on gastric MPO activity was reversed by PD 138,387 (a COX-2 selective inhibitor) and PDTC (an inhibitor of NF-kappaB activation) but not by DMSO (a hydroxyl radical scavenger) and allopurinol (a xanthine oxidase inhibitor). In contrast, increased jejunal MPO activity was blocked by both DMSO, PD 138,387, and PDTC, while allopurinol enhanced it. PD 138,387 and PDTC reduced gastrointestinal mast cell number while DMSO and allopurinol did not Diquat-induced inflammation involves a gastrointestinal NF-kappaB activation and COX-2 dependent proinflammatory prostanoid synthesis. Furthermore, the hydroxyl radical is involved in intestinal but not gastric inflammation.
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PMID:Pathways involved in mild gastrointestinal inflammation induced by a low level exposure to a food contaminant. 1206 6

A rabbit model of chronic ileitis has helped decipher the mechanism of alteration of multiple electrolyte and nutrient malabsorptions in inflammatory bowel disease (IBD). This study examined alterations in the adenosine A1/A3 receptor, oxidant, antioxidant, and immune-inflammatory pathways in chronic ileitis. Chronic ileal inflammation was induced 13-15 days after infection with 10,000 Eimeria magna oocytes. Quantitative analysis in 16 rabbits was done for oxidants, antioxidants, A1 and A3 transcripts, transport, injury, and inflammatory mediators. Inflamed gut had villus blunting, crypt hyperplasia and fusion, and immune cell infiltration. Alkaline phosphatase and Na-glucose co-transport were reduced by 78% (P=0.001) and 89% (P=0.001), respectively. Real-time fluorescence monitoring (TaqMan)-polymerase chain reaction revealed a transcriptional up-regulation of 1.34-fold for A1 and 5.40-fold for A3 receptors in inflamed gut. Lipid peroxidation increased in the mucosa (78%, P=0.012), longitudinal muscle-myenteric plexus (118%, P=0.042), and plasma (104%, P=0.001). Mucosal antioxidants were altered by inflammation: reductions occurred in superoxide dismutase (32%, P=0.001) and catalase (43%, P=0.001), whereas increases occurred in glutathione (75%, P=0.0271) and glutathione reductase (86%, P=0.0007). Oxidant enzyme activities were elevated by 21% for xanthine oxidase (P=0.004), 172% for chloramine (P=0.022), 47% for gelatinase (P=0.041), and 190% for myeloperoxidase (P=0.002). Mast cell tryptase increased by 79% (P=0.006). Increases occurred in the plasma concentration of leukotriene B(4) (13-fold, P=0.003), thromboxane B(2) (61-fold, P=0.018), and tumor necrosis factor-alpha (9-fold, P=0.002). In conclusion, chronic ileitis and tissue injury are associated with discrete alterations in complex multi-level oxidant, antioxidant, and immune inflammatory components. The rabbit ileitis model is a suitable model to gain further insight into chronic inflammation and IBD. We hypothesize that adenosine A3 and A1 receptors may provide a novel target for therapy in chronic ileitis and perhaps IBD.
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PMID:Rabbit chronic ileitis leads to up-regulation of adenosine A1/A3 gene products, oxidative stress, and immune modulation. 1273 66

Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H2O2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H2O2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-alpha levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H2O2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-alpha production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H2O2 production in the small intestine. The H2O2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.
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PMID:Hydrogen peroxide derived from intestine through the mesenteric lymph induces lung edema after surgical stress. 1475 90

Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H2O2 stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC.
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PMID:Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species. 1508 79

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4(+) T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.
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PMID:Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells. 1603 28

Spontaneous bacterial peritonitis is a major cause of mortality after liver cirrhosis. Altered permeability of the mucosa and deficiencies in host immune defenses through bacterial translocation from the intestine due to intestinal bacterial overgrowth have been implicated in the development of this complication. Molecular mechanisms underlying the process are not well known. In order to understand mechanisms involved in translocation of bacteria, this study explored the role of oxidative stress in mediating changes in intestinal mucosal glycosylation and luminal bacterial content during cirrhosis. CCl4-induced cirrhosis in rats led to prolonged oxidative stress in the intestine, accompanied by increased sugar content of both intestinal brush border and surfactant layers. This was accompanied by changes in bacterial flora in the gut, which showed increased hydrophobicity and adherence to the mucosa. Inhibition of xanthine oxidase using sodium tungstate or antioxidant supplementation using vitamin E reversed the oxidative stress, changes in brush border membrane sugar content, and bacterial adherence. In conclusion, oxidative stress in the intestine during cirrhosis alters mucosal glycosylation, accompanied by an increased hydrophobicity of luminal bacteria, enabling increased bacterial adherence onto epithelial cells. This might facilitate translocation across the mucosa, resulting in complications such as spontaneous bacterial peritonitis.
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PMID:Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria. 1655 55

Artichoke (Cynara scolymus L.) leaves have been historically used for the treatment of hyperuricemia and gout, however whether artichoke is truly efficacious for this indication, is still a matter of debate. Thus, the goal of the present study was first to examine the xanthine oxidase (XO) inhibitory activity of an artichoke leaf extract (ALE) and some of its main compounds in vitro and then further test potentially active substances for possible hypouricemic effects using an in vivo rat model. The in vitro study showed that ALE inhibited XO with only minimal inhibitory action (< 5 %) at 100 microg/mL. However, when selected compounds were tested, the caffeic acid derivatives revealed a weak XO inhibitory effect with IC (50) > 100 microM. From the tested flavones the aglycone luteolin potently inhibited XO with an IC (50) value of 1.49 microM. Luteolin 7-O-glucoside and luteolin 7-O-glucuronide showed lower XO inhibition activities with IC (50) values of 19.90 microM and 20.24 microM, respectively. However, oral administration of an aqueous ALE, luteolin, and luteolin 7-O-glucoside did not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate-treated rats. After intraperitoneal injection of luteolin a decrease in uric acid levels was detected suggesting that the hypouricemic effects of luteolin are due to its original form rather than its metabolites produced by the gut flora. In conclusion, an aqueous ALE, caffeic acid derivatives and flavones exerted XO inhibitory effects in vitro but a hypouricemic activity could not be confirmed after oral administration.
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PMID:Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application. 1830 Jan 93

Ischemia-reperfusion (IR) injury is a major insult to postcapillary venules. We hypothesized that IR increases postcapillary venular hydraulic conductivity and that IR-mediated changes in hydraulic conductivity result from temporally and mechanistically separate processes. A microcannulation technique was used to determine hydraulic conductivity (Lp) in rat mesenteric postcapillary venules serially throughout ischemia (45 min) and reperfusion (5 h) induced by superior mesenteric artery occlusion and release. Mesenteric IR resulted in a biphasic increase in Lp. White blood cell (WBC) adhesion slowly increased with maximal adhesion corresponding to the second peak (P < 0.005). After IR, tissue was harvested for RT-PCR analysis of ICAM-1, E-selectin, and P-selectin mRNA. Intercellular adhesion molecule-1 (ICAM-1) mRNA in the gut showed the most significant upregulation. Quantitative real-time PCR revealed that ICAM-1 mRNA was upregulated 60-fold in the gut. An ICAM-1 antibody was therefore used to determine the effect of WBC adhesion on Lp during IR. ICAM-1 inhibition attenuated Lp during the first peak and completely blocked the second peak (P < 0.005). When rats were fed a tungsten diet to inhibit xanthine oxidase and then underwent IR, Lp was dramatically attenuated during the first peak and mildly decreased the second peak (P < 0.005). Inhibition of xanthine oxidase by oxypurinol decreased Lp during IR by over 60% (P < 0.002). Tempol, a superoxide dismutase mimetic, decreased Lp during IR by over 30% (P < 0.01). We conclude that IR induces a biphasic increase in postcapillary hydraulic conductivity. Reactive oxygen species impact both the first transient peak and the sustained second peak. However, the second peak is also dependent on WBC-endothelial cell adhesion. These serial measurements of postcapillary hydraulic conductivity may lead the way for optimal timing of pharmaceutical therapies in IR injury.
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PMID:Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate. 1879 Aug 38

The barrier function of the intestinal mucosa can be disturbed under a variety of pathologic insults. Reactive oxygen species play an important role in intestinal mucosal injury. This in vitro study examines the hypothesis that a free radical scavenger, edaravone (ED), ameliorates gut epithelial permeability increase caused by xanthine oxidase (XO)-mediated oxidative stress in a cell monolayer model. Human intestinal epithelial (HIE) cells were grown as monolayer in bicameral chambers. Twenty milliunits per milliliter of XO+0.25 mM of xanthine (XO+X group) or saline (control) were administered into the basal chambers. Another set of chambers was treated with XO+X and 0.6 mg/ml of ED (XO+X+ED group). The permeability was assessed by quantifying the transepithelial passage of fluorescence in isothiocyanate-labeled dextran. In another series of experiments, Escherichia coli C-25 was also applied in an apical chamber to evaluate the bacterial translocation through the monolayer. The concentration of the fluorescence in isothiocyanate-labeled dextran in the basal chamber of the control group was significantly higher than the control (705 +/- 50.2 vs 155 +/- 45.4 mg/dl, P < .01). Treatment with ED prevented this permeability increase induced by the oxidative stress (P < .01). The incidence of bacterial translocation through the HIE monolayer in XO+X group was also higher than that of the control group (75 vs 13%, P < .05). Increased HIE cell monolayer permeability mediated by xanthine and XO was significantly attenuated with ED. This synthesized radical scavenger may have potential clinical applications against gut mucosal barrier dysfunction.
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PMID:Protective effects of free radical scavenger edaravone against xanthine oxidase-mediated permeability increases in human intestinal epithelial cell monolayer. 1916 3


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