RESUMO
BACKGROUND/AIMS: Induction of acute necrotizing pancreatitis with cerulein causes profound pancreatic glutathione depletion in the mouse. Because cysteine availability can be rate-limiting for glutathione synthesis, the pancreatic content of cysteine during cerulein treatment was measured and the potential benefit of augmenting pancreatic cysteine was determined. METHODS: Female Swiss-Webster mice were treated with cerulein with and without simultaneous administration of the cysteine prodrug, L-2-oxothiazolidine 4-carboxylic acid. Pancreatic cysteine and glutathione content were measured, and serum amylase levels and pancreatic histology were assessed. RESULTS: Pancreatic cysteine content decreased to 42% of normal after 4 hours of cerulein treatment. L-2-oxothiazolidine 4-carboxylic acid more than doubled pancreatic cysteine content at 4 hours and prevented pancreatic cysteine depletion when administered with cerulein. Cerulein caused pancreatic glutathione depletion despite this normalization of cysteine. Moreover, the biochemical and histological evidence of cerulein-induced pancreatitis was unaltered by preventing cysteine depletion. CONCLUSIONS: Pancreatic cysteine is depleted during induction of acute pancreatitis with cerulein in parallel with depletion of pancreatic glutathione. Because preventing pancreatic cysteine depletion with L-2-oxothiazolidine 4-carboxylic acid did not prevent glutathione loss, causes of pancreatic glutathione depletion other than insufficiency of this critical precursor must also play an important role in cerulein-induced glutathione depletion.