Xenobiotic metabolism, oxidant stress and chronic pancreatitis - Focus on glutathione

Chronic pancreatitis, although relatively rare in the Western World, is com mon in certain tropical zones where staple crops such as cassava are rich i n cyanogenic glycosides, This paper reviews the evidence for a cyanide conn ection, with reference to experimental studies using another plant nitrile, crambene; and then examines the hypothesis that chronic pancreatitis repre sents a manifestation of uncoordinated detoxification reactions between pan creatic cytochrome P450 mono-oxygenases and phase II conjugating enzymes, r esulting in the irreversible consumption of glutathione in the acinar cell. The conclusion is that the central role of disrupted pancreatic glutathion e status, as a result of 'xenobiotic stress', in the evolution of chronic p ancreatitis cannot be overestimated. This position contrasts with that in a cute pancreatitis, in which glutathione depletion has a pivotal role too, b ut occurs as a result of 'stress' from reactive oxygen species.