Models of Inflammation: Measuring Gastrointestinal Ulceration in the Rat

Phyllis E. Whiteley1, Stacie A. Dalrymple1

1 Roche Bioscience, Palo Alto, California
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.2
DOI:  10.1002/0471141755.ph1002s00
Online Posting Date:  May, 2001
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Abstract

In rats, nonsteroidal anti‐inflammatory drugs (NSAIDs) such as indomethacin induce gastrointestinal ulcerations. This unit describes a procedure to elicit and measure indomethacin‐induced gastrointestinal lesions. This approach can be used to test for gastrointestinal side effects of potential anti‐inflammatory and other agents.

     
 
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Table of Contents

  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Tables
     
 
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Materials

Basic Protocol 1:

  Materials
  • Female Crl:CD(SD)BR Vaf+ rats weighing 110 to 120 g at the time of arrival (Charles River Labs)
  • Indomethacin (see recipe)
  • Vehicle (see recipe)
  • Test compound
  • 0.9% (w/v) NaCl (Irrigation USP, McGaw)
  • CO 2 supply
  • 1% (w/v) Evan's blue (Sigma) in 0.9% (w/v) NaCl
  • Scales accurate to 0.1 g
  • 1‐ and 3‐ml syringes with Luer‐Lok hubs (Becton Dickinson Labware)
  • 16‐G, 3‐in. gavage needles (Popper & Sons)
  • 25‐G, ⅝‐in. needles (Becton Dickinson Labware)
  • Wire‐bottom cages
  • Sharp dissecting scissors
  • 12‐ml irrigation syringes with tapered curved tip (Monoject)
  • Magnified light (VWR)
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Figures

Videos

Literature Cited

   Jouzeau, J.Y., Terlain, B., Abid, A., Nedelec, E., and Netter, P. 1997. Cyclooxygeanse isoenzymes. How recent findings affect thinking about nonsteroidal anti‐inflammatory drugs. Drugs 53:563‐582.
   Kent, T.H., Cardinelli, R.M., and Stamler, F.W. 1969. Small intestinal ulcers and intestinal flora in rats given indomethacin. Am. J. Pathol. 54:237‐249.
   Masferrer, J.L., Zweifel, B.S., Manning, P.T., Hauser, S.D., Leahy, K.M., Smith, W.G., Isakson, P.C., and Seibert, K. 1994. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. U.S.A. 91:3228‐3232.
   Olds, R.J. 1979. A Color Atlas of the Rat: Dissection Guide. John Wiley & Sons, New York.
Key Reference
   Young, J.M. and Yee, J.P. 1994. In Non‐steroidal Anti‐Inflammatory Drugs:Mechanisms and Clinical Uses. (A.J. Lewisand D.E. Furst, eds.) pp. 247‐266. Marcel Dekker, New York.
  A good review on the NSAIDs and rat ulcerogenesis.
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