Dietary nucleotides augment dextran sulfate sodium-induced distal colitis in rats

We have previously shown that enteral and parenteral supplementation of nuc leotides (NT) accelerates healing of small-bowel ulcers in rats with indome thacin-induced ileitis. The purpose of this study was to evaluate whether d ietary NT supplementation would similarly affect ulcer healing in dextran s ulfate sodium (DSS)-induced colitis in rats. Male Sprague-Dawley rats were randomly assigned to receive either nucleotide-free (NF) or NT-supplemented diets. After 2 d of prefeeding, colitis was induced by including 40 g/L of DSS in drinking water for 3 d, followed thereafter by tap water. Rats from each group were killed at 7 and 12 d after induction of colitis. Additiona l rats were also used for both the groups as controls (untreated groups). T he length of colon was measured and evaluated by histological score. Coloni c myeloperoxidase (MPO) activity was assessed. In a separate series of expe riments, rats were studied at 0, 4, 7, and 12 d for interleukin-1 beta (IL- 1 beta) in rectal dialysate and plasma. Ulceration predominated in the dist al colon in DSS-treated rats. There was no significant difference between t he histological scores of the NF and NT-supplemented groups either at 7 or 12 d. MPO activity at 7 and 12 d was significantly higher in the NT-supplem ented compared to NF group (7 d: 1013 +/- 172 vs. 409.9 +/- 103.2; 12 d: 47 1.9 +/- 112.4 vs. 223.6 +/- 21.6 units . min(-1) . g colon(-1)). IL-1 beta concentration in rectal dialysate was significantly higher at 7 d in both g roups compared to 0 and 4 d. At 12 d it continued to be significantly eleva ted in the NT-supplemented group and was greater than in the NT-free group. Our data on the proinflammatory cytokine, in conjunction with MPO activity , strongly suggest that NT supplementation aggravates the severity of DSS-i nduced colitis in rats.