Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that enhanced release of free oxygen radicals plays an important role in the pathogenesis of acute pancreatitis. Therefore, we studied the activity of the oxygen radical generating xanthine oxidase (XOD) in pancreatic tissue from rats treated with either dibutyltin dichloride/ethanol (DBTC/EtOH: 6 mg kg-1/13.7 mg kg-1, i.v.), ethanol alone (EtOH: 13.7 mmol kg-1, i.v.), or isotonic saline (NaCl) as control. We also investigated activities of the oxygen radical scavengers superoxide dismutase (SOD) and glutathione peroxidase (GPX). In addition, levels of the lipid peroxidation marker malondialdehyde (MDA) were determined. Enhanced activity of XOD was not detected. While SOD activity 1 and 6 h after treatment was significantly more reduced by DBTC/EtOH than by EtOH alone, no difference was found thereafter. Correspondingly, both regimens diminished GPX activity. Moreover, DBTC/EtOH and EtOH rapidly increased MDA levels within 1 h, indicating release of oxygen radicals early on after administration. After 16 h the MDA concentration was still elevated only in the DBTC/EtOH group. Although similar metabolic alterations were observed in both groups, only DBTC/EtOH induced acute interstitial pancreatitis within 24 h. We conclude that (a) a tissue imbalance between oxidants and antioxidants might be of importance in the pathogenesis of DBTC/EtOH-induced acute interstitial pancreatitis; (b) although EtOH increases oxygen radical levels, additional damage is required for development of acute pancreatitis; (c) XOD does not seem to be responsible for significant oxygen radical generation; and (d) the DBTC/EtOH model is a useful tool to study acute interstitial pancreatitis in rats.
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PMID:Oxygen radical generation and acute pancreatitis: effects of dibutyltin dichloride/ethanol and ethanol on rat pancreas. 853 55

The involvement of active oxygen has been suggested in the development of cerulein-induced acute pancreatitis in rats. Previously, we directly detected pancreatic active oxygen (O2-) production in rats with cerulein-induced pancreatitis by using a supersensitive photon counter and a cypridina luciferin analogue (MCLA) that reacts specifically with O2- by emitting luminescence. In the present study, with the specific aim of determining the source of O2-, we prepared two groups of animals with cerulein-induced pancreatitis: those treated with allopurinol, a xanthine oxidase inhibitor; and those treated with nitrogen mustard, a leukopenia-inducing substance. In each of these two groups, pancreatic O2- production and the severity of pancreatic injuries were comparatively studied. In the leukopenic animal group, decreases in O2- dependent chemiluminescence and improvement in the pancreatic condition coincided. This suggests that neutrophils might be involved in experimentally induced pancreatitis as a source of active oxygen.
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PMID:The involvement and sources of active oxygen in experimentally induced acute pancreatitis. 872 Jun 65

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800+/-3813 vs 6382+/-184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00+/-1.75 vs 0.28+/-0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631+/-2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55+/-0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.
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PMID:Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis. 972 67

In the present study we evaluate the possibility that xanthine oxidase released by damaged pancreas could act as a source of oxidative damage in systemic tissues during the early stages of acute pancreatitis. This was accomplished by evaluating the effects of xanthine oxidase inhibition with oxypurinol infused into the portal vein. Under these conditions, we inhibited the enzyme before it reached the liver and other distant organs, without inducing changes in the severity of pancreatic damage. Results indicate that pancreatitis parallels increases in xanthine oxidase activity in plasma. Superoxide radicals generated by this enzyme appears to be involved in the decrease of reduced glutathione levels in the plasma and liver. In addition, xanthine oxidase inhibition prevents the infiltration of neutrophils into the lungs. We conclude that oxygen free radicals generated by xanthine and xanthine oxidase released to the bloodstream are involved in the systemic organ failure associated with acute pancreatitis.
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PMID:Free radicals generated by xanthine oxidase mediate pancreatitis-associated organ failure. 982 26

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.
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PMID:The role of polymorphonuclear leukocytes and oxygen-derived free radicals in experimental acute pancreatitis: mediators of local destruction and activators of inflammation. 1056 9

The present work critically reviews the evidence for an involvement of free radicals in the pathophysiology of acute pancreatitis and the potential of treatment with antioxidants and scavenger substances. Data originating from clinical trials, experimental pancreatitis studies and in vitro investigations are included. Enhanced free radical activities and increased concentrations of lipid peroxides in plasma and tissue have been found in both patients and experimental animals with acute pancreatitis. The individual contribution of possible sources of free radicals (e.g., invading inflammatory cells, xanthine oxidase, cytochromes P450, nitric oxide synthase) is not yet clear, however. Since prophylactic administration of antioxidants diminished, in particular, pancreatic edema formation, free radicals seem to play an important role in the genesis of edema in acute pancreatitis. An involvement of free radicals in the pathogenesis of pancreatic necrosis could not yet be proven. Thus, no antioxidant treatment has proven useful for therapy of fulminant pancreatitis in animals to date. However, in severe acute pancreatitis characterized by death occurring after 12-18 hours, the seleno-organic compound Ebselen, which has a glutathione peroxidase-like activity, and the membrane permeable ascorbic acid derivative CV-3611 have been demonstrated to be effective. To date, controlled clinical studies have failed to demonstrate the therapeutic efficacy of antioxidant selenium or glutathione precursor supplementation. Therefore, further controlled clinical trials are needed to determine whether supplements of antioxidants can alter the clinical course of acute pancreatitis. Since the nitric oxide radical may even protect the pancreas, a purely negative discussion of the role of free radicals on the pancreas is not justified. The actual role of free radicals in acute pancreatitis, i.e. serving the body's defense against infection, being an epiphenomenon of the inflammatory process without pathophysiological relevance, or having true pathogenic significance, is not yet clear. Lipid peroxidation may perhaps not be the cause but rather the sequel of pancreatic inflammation and may likely reflect the severity of the systemic inflammatory response rather than that of pancreatic parenchyma damage. In vitro, exposure of isolated pancreatic acinar cells to oxidative stress caused rapid cell damage and death. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective therapies in the experimental animal, as well as in patients suffering from pancreatitis. Thus, to further clarify the role of oxidative stress in acute pancreatitis, an integrated approach is needed, including investigations at various biological levels, from isolated cells or even organelles to laboratory animals and, finally, clinical studies in man.
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PMID:Oxidative stress in acute pancreatitis. 1057 39

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.
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PMID:The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin. 1076 88

P-selectin and circulating xanthine oxidase are involved in the process of neutrophil infiltration into the lung associated with acute pancreatitis. This study investigated the mediators that trigger the upregulation of P-selectin in this process. Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. P-selectin expression was measured using radiolabeled antibodies. Neutrophil infiltration and PAF levels were also evaluated. The role of superoxide radical, H(2)O(2), or the enzyme poly (ADP-ribose) synthetase (PARS) on these processes was determined in groups of animals treated with the corresponding inhibitors. Pancreatitis was associated with an increase in P-selectin expression in the lung. Inhibition of PARS or H(2)O(2) abrogated P-selectin upregulation, PAF generation, and neutrophil recruitment. Superoxide dismutation prevented neutrophil recruitment and PAF generation, but had no effect on P-selectin expression. We conclude that during acute pancreatitis, upregulation of P-selectin in the pulmonary endothelium is triggered by H(2)O(2) and PARS activity.
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PMID:H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis. 1088 59

The aim of this work was to evaluate the systemic Hsp72 expression in rat lung and liver in vivo in a model of acute pancreatitis and investigate the possible involvement of xanthine oxidase and neutrophils in this process. Pancreatitis was induced by intraductal administration of 5% sodium taurocholate and samples of lung and liver were obtained 1 and 3 h later. In some groups of rats circulating xanthine oxidase was inhibited with oxypurinol, and neutrophil recruitment was blocked with a monoclonal antibody against P-selectin. Hsp72 expression was assessed by means of Western blot and immunohistochemistry. Results showed Hsp72 induction in lung, but not in liver, shortly after pancreatitis. Hsp72-induced expression was located in bronchial epithelium, alveolar macrophages, infiltrating neutrophils, and blood vessels. Oxypurinol and the antibody against P-selectin prevented pancreatitis-induced lung Hsp72 overexpression suggesting that Hsp72 induction is mediated by neutrophil infiltration into the lungs.
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PMID:Pancreatitis induces HSP72 in the lung: role of neutrophils and xanthine oxidase. 1089 74

The objective of this study was to analyze whether acute pancreatitis leads to changes in the lipid composition and susceptibility to lipid peroxidation of pancreatic membranes. Total lipids, cholesterol, phospholipids, FA, and lipid peroxidation were determined in the pancreatic tissue of rats treated with cerulein and of control rats. In pancreatitic rats, significant decreases in membrane total phospholipid contents (P < 0.05) and in choline and ethanolamine glycerophospholipid levels (P < 0.05 and P < 0.01, respectively), with concomitant significantly higher values of their lysoderivative forms, were found. The cholesterol/phospholipid molar ratio increased by 26%. The unsaturation index of the FA profile decreased significantly (P < 0.01) as a consequence of a decrease in the arachidonic acid content. Incubation of membranes with xanthine oxidase/hypoxanthine-Fe2+/ADP resulted in an increase in the production of TBARS in pancreatitic rats compared to controls. In summary, acute pancreatitis causes changes in the lipid composition of rat pancreatic crude membranes and a greater susceptibility of these membranes to lipid peroxidation.
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PMID:Acute pancreatitis decreases pancreas phospholipid levels and increases susceptibility to lipid peroxidation in rat pancreas. 1190 8


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