Beneficial effects of L-2-oxothiazolidine-4-carboxylate on cerulein pancreatitis in mice

Background & Aims: 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 mu g/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 thief 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.