Beneficial effects of L-2-oxothiazolidine-4-carboxylate on cerulein pancreatitis in mice.
OBJECTIVE
Disturbances of the thiol metabolism of acinar cells may play a role in the pathophysiology of acute pancreatitis. Cerulein-induced pancreatitis causes depletion of glutathione. The entire pancreatic thiol status was assessed in this model. The potential benefit of augmentation of pancreatic glutathione by L-2-oxothiazolidine-4-carboxylate (OTC) for the course of pancreatitis was determined.


METHODS
Mice were treated with cerulein (50 microg/kg) and with or without administration of OTC (6.5 and 20 mmol/kg, respectively). Pancreatic tissue was analyzed for reduced and oxidized glutathione, nonprotein thiol, mixed disulfide, protein thiol, and protein disulfide. Histopathology and serum amylase were also assessed.


RESULTS
Levels of all thiol compounds were altered profoundly at a different rate during pancreatitis. OTC caused an increase of 60% in pancreatic glutathione. Its administration at 20 mmol/kg attenuated the decrease of pancreatic glutathione and protein thiol until 8 hours and blunted the cerulein-induced increase in amylase activity and histopathologic damage. At 6.5 mmol/kg, OTC failed to show effects on all parameters.


CONCLUSIONS
OTC administered in a prophylactic protocol dose-dependently exerted beneficial effects in cerulein-induced pancreatitis in mice despite only transient influence on pancreatic thiol compounds. Thiols (e.g., reduced glutathione) and their corresponding disulfides are critically involved in the pathophysiology of cerulein-induced pancreatitis.
Lüthen
R
R
Department of Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
Grendell
J H
JH
Häussinger
D
D
Niederau
C
C
D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide; D004220:Disulfides / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D051379:Mice; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D011761:Pyrrolidonecarboxylic Acid; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012016:Reference Values; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D004220:Disulfides; D011949:Receptors, Cholecystokinin; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D053778:Thiazolidines; D002108:Ceruletide; D000681:Amylases; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D019803:Glutathione Disulfide; C029536:2-oxothiazolidine-4-carboxylic acid