Digestive Diseases and Sciences

, Volume 50, Issue 3, pp 565–573 | Cite as

Inhibition of Clostridium difficile Toxin A–Induced Colitis in Rats by APAZA

  • Douglas C. Mcvey
  • Rodger A. Liddle
  • Jennifer y
  • Nnochiri Ekwuribe
  • Steven R. Vigna
Article

Abstract

A new compound, APAZA, consisting of a molecule of 5-aminosalicylic acid linked to one molecule of 4-aminophenylacetic acid by an azo bond, was tested for its ability to inhibit acute colitis in rats caused by Clostridium difficile toxin A. When administered chronically for 5 days in drinking water, APAZA significantly inhibited toxin A–induced myeloperoxidase activity, luminal fluid accumulation, and structural damage to the colon at doses of from 1 to 100 mg/kg⋅day. For comparison, sulfasalazine was administered in identical doses and was found to significantly inhibit toxin A–induced colitis only at the dose of 100 mg/kg⋅day. When 4-aminophenylacetic acid alone was administered chronically in drinking water, it also inhibited toxin A–induced colonic inflammation at a dose of 100 mg/kg⋅day. In order to determine if 4-aminophenylacetic acid has a direct anti-inflammatory effect on the colon rather than a systemic effect, 4-aminophenylacetic acid was administered acutely to surgically prepared isolated colonic segments by intraluminal injection in anesthetized rats 30 min before toxin A was injected. 4-Aminophenylacetic acid strongly and significantly inhibited toxin A–induced colitis in this experiment at doses as low as 10 μg/segment. It is concluded that APAZA is a potent inhibitor of toxin A–induced colonic inflammation in rats and that its constituent, 4-aminophenylacetic acid, is responsible for this increased protection against colitis compared to the 5-aminosalicylic acid component of sulfasalazine.

Keywords:

5-aminosalicylic acid 4-aminophenylacetic acid inflammation colitis animal model. 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Douglas C. Mcvey
    • 1
    • 3
  • Rodger A. Liddle
    • 1
    • 3
  • Jennifer y
    • 4
  • Nnochiri Ekwuribe
    • 4
  • Steven R. Vigna
    • 1
    • 2
    • 3
    • 5
  1. 1.Departments of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Departments of Cell BiologyDuke University Medical CenterDurhamUSA
  3. 3.V.A. Medical CenterDurhamUSA
  4. 4.NOBEX CorporationUSA
  5. 5.V.A. Medical Center/151-HDurhamUSA

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