The acute pancreatotoxic effects of the plant nitrile 1-cyano-2-hydroxy-3-butene.
The effects of synthetic 1-cyano-2-hydroxy-3-butene (CHB), a racemic mixture of the (R)- and (S)-enantiomers, were studied in adult male rats. The compound given by gavage in olive oil at doses of 25-200 mg/kg causes toxic effects on the pancreas that resemble those seen when naturally occurring CHB is given to rats. At 6 h after dosing, pancreatic edema is seen with doses of 100 mg/kg and greater. The edema fluid had a high protein content, indicating a marked increase in macromolecular permeability of the pancreatic microcirculation. A loss of zymogen granules from the acinar cells and a lacy supranuclear vacuolation of the acinar cell cytoplasm was observed. At 4 h after dosing, pancreatic nonprotein thiols were depleted and rebounded at 24 h to three times control values. At 120 h nonprotein thiol levels decreased but were still elevated compared with control values. Glutathione-S-transferase activity in the pancreas had a similar pattern of change with initial reduction, followed by elevation at 24 h. In rats with pancreatic and biliary fistulas, intraduodenal CHB caused a transient early stimulation of pancreatic juice secretion followed by a return to control values in the case of the lower doses of CHB and depression of flows at larger doses. All doses of CHB caused a dose-related depression of protein concentration in pancreatic juice. Pancreatic juice flow was almost abolished at doses of 200 mg/kg. CHB caused a dose-dependent choleresis accompanied by a marked reduction in bile acid concentrations in bile.(ABSTRACT TRUNCATED AT 250 WORDS)
Maher
M
M
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Chernenko
G
G
Barrowman
J A
JA
D000208:Acute Disease; D000475:Alkenes / Q000633:toxicity*; D000818:Animals; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D010182:Pancreatic Diseases / Q000139:chemically induced*; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000475:Alkenes; D009570:Nitriles; D010936:Plant Extracts; C055903:1-cyano-2-hydroxy-3-butene; D005982:Glutathione Transferase; D005978:Glutathione