Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present work reviews the evidence for an involvement of free radicals in the pathophysiology of chronic pancreatitis and the potential of treatment with antioxidant and scavenger substances. Preliminary results indicate that exposure of isolated pancreatic acinar cells to a reaction mixture containing hypoxanthine, xanthine oxidase, and chelated iron causes cell damage and death probably due to generation of superoxide anion and hydrogen peroxide. It still needs to be analyzed which scavengers and antioxidants are able to ameliorate the damage due to oxidant stress in cell models. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective antioxidants and scavengers in the experimental animal and in patients with pancreatitis. As yet there are no published studies about the role of free radicals in animal models of chronic pancreatitis. This fact is probably due to the shortcomings of the animal models available. Recent studies presented evidence that activation of oxygen-derived free radicals occurs in patients with chronic pancreatitis. There is also some evidence that the dietary intake of antioxidants may be reduced in patients with chronic pancreatitis. It was suggested that such reduction of antioxidant defenses in the face of an increased demand due to heightened induction of P450 activities may facilitate lipid peroxidation. However, as yet, there is no direct evidence that a reduction of dietary antioxidants with a simultaneous increase in P450 activity is the primary mechanism which initiates chronic pancreatitis without contribution of other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of free radicals in the pathophysiology of chronic pancreatitis: potential of treatment with antioxidant and scavenger substances. 179 74

Oxidative stress is regarded a major factor in the pathogenesis of both acute and chronic pancreatitis. The mechanisms by which free radicals damage the acinar cells are not yet clear. Standard models of oxidative stress were applied to investigate the susceptibility of isolated rat pancreatic acinar cells and zymogen granules to oxidant attack and to explore the potential of several antioxidants and radical scavengers to prevent such injury. Short-term peak production of free radicals by xanthine oxidase was more injurious to the acinar cells than continual radical generation at a lower level by iron/adenosine diphosphate. Isolated zymogen granules were much more susceptible to oxidative damage that isolated acinar cells. In both models, a combination of catalase and superoxide dismutase effectively prevented cell damage. In contrast, the classical hydroxyl radical scavengers mannitol, dimethyl sulphoxide and dimethyl thiourea, as well as the iron chelator deferoxamine were ineffective and at a higher concentration were even toxic. The novel low molecular weight 21-aminosteroid substances called "lazaroids" showed a highly protective potential when applied at a concentration of 1-50 mumol/l and are therefore considered to be the substances most likely to protect the pancreas cells against oxidative injury. Higher concentrations of the lazaroids, however, also caused additional damage to the cells. The results indicate that multiple radical species and several mechanisms are involved in oxidative injury to the pancreatic acinar cell. From present in vitro data, no single substance can be recommended for use in animal experiments or human studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative stress-induced changes in pancreatic acinar cells: insights from in vitro studies. 795 63