Document Detail

Cerulein-induced pancreatic cysteine depletion: prevention does not diminish acute pancreatitis in the mouse.
MedLine Citation:
PMID:  8076769     Owner:  NLM     Status:  MEDLINE    
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.
B A Neuschwander-Tetri; M Barnidge; C G Janney
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Gastroenterology     Volume:  107     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-09-30     Completed Date:  1994-09-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  824-30     Citation Subset:  AIM; IM    
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri.
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MeSH Terms
Caerulein / pharmacology*
Cysteine / deficiency*,  metabolism
Dose-Response Relationship, Drug
Glutathione / deficiency
Mice, Inbred Strains
Pancreas / drug effects,  metabolism*
Pancreatitis / chemically induced,  metabolism
Pyrrolidonecarboxylic Acid
Thiazoles / pharmacology
Time Factors
Reg. No./Substance:
0/Thiazoles; 0/Thiazolidines; 17650-98-5/Caerulein; 19750-45-9/2-oxothiazolidine-4-carboxylic acid; 52-90-4/Cysteine; 70-18-8/Glutathione; 98-79-3/Pyrrolidonecarboxylic Acid
Comment In:
Gastroenterology. 1994 Sep;107(3):888-92   [PMID:  8076778 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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