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)

It has been suggested that oxygen-derived free radicals play a decisive role in the pathogenesis of acute experimental pancreatitis in a model of edematous pancreatitis. Accordingly, allopurinol, a xanthine oxidase inhibitor, was shown to mitigate the development of nonfatal acute pancreatitis in ex vivo perfusion models using dogs. For further evaluation of allopurinol, its effect was studied in two forms of fatal necrotizing acute experimental pancreatitis: sodium taurocholate-induced pancreatitis in rats and choline-deficient ethionine-supplemented diet-induced pancreatitis in mice. Allopurinol did not affect the mortality rate, pancreatic enzyme elevation in serum and ascites, the enzyme content of the pancreas, or any parameter indicating histopathological damage in the pancreas. Although these experiments did not determine the role oxygen-derived free radicals play in the development of pancreatitis, they show, none the less, the absence of any beneficial therapeutic effect of a xanthine oxidase like allopurinol on the development of the disease once it has begun.
Pancreas 1989
PMID:Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice. 276 73

Lazaroids, 21-aminosteroids without gluco- and mineralocorticoid activity, protect against oxidative injury in nervous system cells and may therefore also have a potential for treatment of pancreatitis, where oxidative stress contributes to cell injury. The present study evaluates the protective potential of the lazaroids U-78518F, U-74500A, and U-74389F against damage to isolated pancreatic acinar cells exposed to two models of oxidative stress: (a) a XOD/HX model, consisting of xanthine oxidase, hypoxanthine, and chelated FeCl3; and (b) an ADP/Fe model, consisting of FeSO4 and the reducing agent ADP. Both models caused time-dependent cell injury as assessed by uptake of trypan blue and release of lactate dehydrogenase. Short-term peak production of free radicals in the XOD/HX model--as monitored by the deoxyribose assay--was more injurious to cells than continuous radical generation at lower levels in the ADP/Fe model. In general, lazaroids at 1-10 microM reduced oxidative damage and deoxyribose oxidation in both models. The degree of reduction of cell damage and deoxyribose oxidation depended on the type and concentration of the lazaroid and the model used. Lazaroid concentrations < 0.1 microM were ineffective, and concentrations > 50 microM even accelerated cell injury, although lazaroids still served as scavengers at high concentrations. At least part of the noxious effects of high lazaroid concentrations is due to nonspecific membrane damage because these concentrations caused cell injury also in the absence of oxidative stress. The limited range of protective concentrations has to be observed in further in vivo studies. Interestingly, acinar cells in the absence of lazaroids also reduced radical-induced deoxyribose degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1995 Aug
PMID:Lazaroids protect isolated rat pancreatic acinar cells against damage induced by free radicals. 747 66

Intralobular oxygen radical formation was examined in cerulein-stimulated rat pancreatic acinar cells by digital imaging microscopic fluorography using a hydroperoxide-sensitive fluorescent probe, dichlorofluorescin (DCFH) diacetate. The isolated pancreatic acinar cells loaded with DCFH diacetate were microscopically observed, and the dichlorofluorescein (DCF) fluorescence yielded by DCFH oxidation via hydroperoxides was digitally processed. Within the initial 20 min after the application of cerulein (10 microM), intracellular oxidative stress was observed as indicated by the increase in DCF fluorescence intensity and reached its maximum at 60 min. DCF fluorescence intensity was then gradually decreased until 80 min, followed by a marked increase in propidium iodide (PI) fluorescence, suggesting irreversible cell death. Allopurinol (1 microM), a xanthine oxidase inhibitor, significantly attenuated the early increase of DCF fluorescence intensity as well as the late cell damage. Treatment with hyperbaric oxygen (PO2 300 mm Hg) also significantly attenuated both the increase of DCF fluorescence and the number of PI-positive cells. The results suggest that xanthine oxidase-mediated oxygen radicals may play an important role in cerulein-induced intracellular oxidative stress in pancreatic acinar cells of rats.
Pancreas 1993 Jul
PMID:Xanthine oxidase-mediated intracellular oxidative stress in response to cerulein in rat pancreatic acinar cells. 836 67

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.
Pancreas 1995 Nov
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.
Pancreas 1996 Mar
PMID:The involvement and sources of active oxygen in experimentally induced acute pancreatitis. 872 Jun 65

Oxidants and their generator, xanthine oxidase (XO), play a major role in the damaging of the structural and functional integrity of the lung. Such damage has been recently demonstrated in the presence of pancreas ischemia-reperfusion (IR). We investigated whether mannitol, a clinically used agent and antioxidant, prevented lung damage after pancreas IR. Rats (n = 48) were anesthetized, after which each pancreas was isolated and perfused (controls), or made ischemic (IR) for 40 min, or made ischemic and treated upon reperfusion with four different doses of mannitol administered in the perfusate (8 replicates/group). Ischemia was followed by in-series 15-min pancreas plus normal isolated lung reperfusion. Isolated lungs were subsequently perfused for 45 min with the 15-min accumulated effluents. Pancreas injury occurred in all IR organs as demonstrated by abnormal reperfusion pressure, the wet-to-dry ratio, amylase and lipase leakage into the circulation, and XO activity and reduced glutathione (GSH) pool in the tissues. Pulmonary plateau pressure increased by 80%, and final PO(2)/FiO(2) decreased by 28% in the IR-untreated paired lungs. Bronchoalveolar lavage volume increased by 50% and 2- to 8-fold increase in their contained XO and GSH were recorded as well. The above indices of injury in lungs perfused with 0.77 mM mannitol were the least detected, compared with negligible efficacy of other (0.55 < 0.22 < 1.1 mM) dosages. Amylase and lipase did not contribute to lung injury. Ex vivo acute pancreatitis induces acute lung injury via oxidants/antioxidants imbalance, which is preventable by mannitol.
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PMID:Mannitol prevents acute lung injury after pancreas ischemia-reperfusion: a dose-response, ex vivo study. 1953 32