Glutathione depletion with L-buthionine-(S, R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfo...

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Bibliographic Details
Published in:Digestive diseases and sciences 2002-08, Vol.47 (8), p.1793-1799
Main Authors: ALSFASSER, G, GOCK, M, HERZOG, L, GEBHARD, M. M, HERFARTH, C, KLAR, E, SCHMIDT, J
Format: Article
Language:English
Subjects:
Acute Disease
Amylases - metabolism
Animals
Biological and medical sciences
Buthionine Sulfoximine - adverse effects
Buthionine Sulfoximine - pharmacology
Ceruletide - pharmacology
Digestive system
Enzyme Inhibitors - pharmacology
Glutathione - biosynthesis
Glycodeoxycholic Acid
In Vitro Techniques
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Pancreas - drug effects
Pancreas - metabolism
Pancreatitis, Acute Necrotizing - chemically induced
Pancreatitis, Acute Necrotizing - physiopathology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Rats
Rats, Wistar
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Summary:A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.
ISSN:0163-2116
1573-2568
DOI:10.1023/A:1016496612906