The effect of L-buthionine-[S,R]-sulfoximine on the pancreas in mice. A model of weakening glutathione-based defense mechanisms.

L-Buthionine-[S,R]-Sulfoximine (BSO) decreases glutathione levels in various organs by inhibition of gamma-glutamylcysteine synthetase. We have examined the levels of total glutathione and oxidized glutathione in the pancreas of mice, as well as serum amylase and pancreatic histology, after BSO administration in two different ways. The injection of a single dose of BSO (5 mmol/kg body wt) decreased total glutathione to 10% of the control value. A similar depletion was observed after 24 h of oral administration of a 10 mM BSO solution, without changes in the levels of oxidized glutathione. BSO-induced pancreatic glutathione depletion--even if maintained for up to 14 d--did not cause morphological alterations of the pancreas or hyperamylasemia. Thus pancreatic glutathione depletion in itself does not lead to pancreatitis, although during development of experimental acute pancreatitis, glutathione depletion has been described. BSO might be used in animal models to weaken the glutathione-based acinar defense mechanisms against oxidant stress or to alter other physiologic processes in which glutathione is involved.