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

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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.

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Correspondence to Steven R. Vigna PhD.

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Mcvey, D.C., Liddle, R.A., y, J. et al. Inhibition of Clostridium difficile Toxin A–Induced Colitis in Rats by APAZA. Dig Dis Sci 50, 565–573 (2005). https://doi.org/10.1007/s10620-005-2476-1

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  • DOI: https://doi.org/10.1007/s10620-005-2476-1

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