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Indomethacin and Pancreatic Enzymes Synergistically Damage Intestine of Rats

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Abstract

The use of high-dose pancreatic enzymes bypatients with cystic fibrosis was associated with thedevelopment of fibrosing colonopathy. Preliminarystudies indicated that the infusion of high-dosepancreatic enzymes alone did not cause intestinal damage.We hypothesized that cystic fibrosis patients thatdeveloped fibrosing colonopathy had increased intestinalpermeability. Our goal was to develop a rat model for pancreatic enzyme-induced fibrosingcolonopathy by increasing intestinal permeability withthe use of indomethacin. Pancreatic enzymes, 150,000units/kg/day, and indomethacin, 3 mg/kg/day, alone and in combination were administered via duodenalcatheter to rats for 10 days. Indomethacin andpancreatic enzymes caused intestinal damage, resultingin significant increases in the total number of ulcers (P < 0.007), the number of severe ulcers (P< 0.003), and ulcers in the cecum and colon (P <0.0007). We conclude that the combination ofindomethacin and pancreatic enzymes acts synergistically to cause damage to the intestine.

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Authors
  1. Robert E. Kimura
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  2. Valerie Arango
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  3. John Lloyd-Still
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Kimura, R.E., Arango, V. & Lloyd-Still, J. Indomethacin and Pancreatic Enzymes Synergistically Damage Intestine of Rats. Dig Dis Sci 43, 2322–2332 (1998). https://doi.org/10.1023/A:1026691227845

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