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 testedfor 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 x 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 x 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 x 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 microg/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.