Oxidative stress-induced changes in pancreatic acinar cells: insights from in vitro studies

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)