THE EFFECT OF INTESTINAL PERMEABILITY ON PANCREATIC ENZYME-INDUCED ENTEROPATHY IN THE RAT

Background: Fibrosing colonopathy in cystic fibrosis occurs in childre n 2 to 7 years old and is associated with excess doses of high and reg ular 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 stu died after administration of different combinations of pancreatic enzy mes, oleic acid, and reserpine. Results: Pancreatic enzymes alone prod uced 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 i ntestinal eosinophilia and necrosis of the jejunoileal muscle layer an d inflammatory nodules in the liver, which increased with duration of insult. Conclusions: Increased intestinal permeability potentiates dam age to the intestine caused by excessive pancreatic enzyme dosage. It is a characteristic of cystic fibrosis that may increase vulnerability to fibrosing colonopathy.