The effect of intestinal permeability on pancreatic enzyme-induced enteropathy in the rat.
BACKGROUND
Fibrosing colonopathy in cystic fibrosis occurs in children 2 to 7 years old and is associated with excess doses of high and regular strength lipase pancreatic enzymes, given for more than 6 months. A rat model was developed to study the effects of excessive doses of pancreatic enzymes equivalent to those producing fibrosing colonopathy in cystic fibrosis patients.


METHODS
Five groups of animals were studied after administration of different combinations of pancreatic enzymes, oleic acid, and reserpine.


RESULTS
Pancreatic enzymes alone produced minimal damage to the intestine and none to the liver. Excessive doses of pancreatic enzymes in combination with agents that increased intestinal permeability (oleic acid, reserpine) were associated with intestinal eosinophilia and necrosis of the jejunoileal muscle layer and inflammatory nodules in the liver, which increased with duration of insult.


CONCLUSIONS
Increased intestinal permeability potentiates damage to the intestine caused by excessive pancreatic enzyme dosage. It is a characteristic of cystic fibrosis that may increase vulnerability to fibrosing colonopathy.
Lloyd-Still
J D
JD
Department of Pediatrics, Rush Medical College, Chicago, Illinois, USA.
Uhing
M R
MR
Arango
V
V
Fusaro
A
A
Kimura
R E
RE
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004802:Eosinophilia / Q000139:chemically induced; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007422:Intestines / Q000473:pathology / Q000503:physiopathology*; D008049:Lipase / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000473:pathology; D009336:Necrosis; D019301:Oleic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology
D019301:Oleic Acid; D012110:Reserpine; D008049:Lipase