EFFECT OF LEUKOTRIENE C4D4 ANTAGONIST ON COLONIC DAMAGE-INDUCED BY INTRACOLONIC ADMINISTRATION OF TRINITROBENZENE SULFONIC-ACID IN RATS

We examined the effects of eicosanoid antagonists on colonic damage in duced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bow el model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given i ntrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 an tagonist), ONO-4057 (a leukotriene B-4 antagonist), and OKY-046 (a thr omboxane A(2) synthetase inhibitor) were given to obtain the same bloo d level, either 4h before (pre-treatment model) or 24 h after (the pos t-treatment model) the administration of TNB (n = 8 in all groups). Dr ugs were given once daily for 6 days through a gastric feeding tube. A utopsy was performed on the 7th day. Colonic damage was assessed in te rms of colonic damage scores, and myeloperoxidase (MPO) activity and e icosanoid concentrations in colonic tissues were measured. Compared wi th the group given TNB alone, the colonic damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not re duced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C-4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated tha t a leukotriene C4D4 antagonist reduced colonic inflammation; however, its anti-inflammatory effect was limited in this colitis model.