INTRAVENOUS NUCLEOSIDES AND A NUCLEOTIDE PROMOTE HEALING OF SMALL-BOWEL ULCERS IN EXPERIMENTAL ENTEROCOLITIS

Our aim was to evaluate the possible beneficial effect of intravenous nucleosides and a nucleotide in healing small bowel ulceration in a ra t model of enterocolitis. Fourteen Lewis female rats were randomized i nto total parenteral nutrition (TPN, N = 7) and TPN + nucleosides and a nucleotide (NS/NT, N = 7) groups. After adaptation, two doses of ind omethacin (7.5 mg/kg) were administered subcutaneously 24 hr apart to each animal in both groups. Concomitant with the first dose of indomet hacin, TPN or TPN + NS/NT were infused for four days. The TPN and TPN + NS/NT were isocaloric and isonitrsgenous. At the end of four days, t otal ulcer length in the entire small bowel was measured. The mucosa s urrounding ulcers was studied by optical microscopy. Immunohistochemis try was performed for proliferating cell nuclear antigen (PCNA). Ileal crypt and villus lengths were measured with an eyepiece micrometer, c rypt-villus ratios were calculated, and crypt mitotic index and percen tage of PCNA-labeled cells determined to assess cellular proliferation . Total ulcer length decreased significantly in the TPN + NS/NT group compared to the TPN group (42 vs 76 mm). In the TPN + NS/NT versus TPN group, the ileal mucosa surrounding ulcers showed significantly great er crypt length (21%) and there was increased crypt-villus ratio (0.53 vs 0.39), crypt mitotic index (1.2 vs 0.9), and PCNA labeling (43% vs 30%). We conclude that in rats with indomethacin-induced enterocoliti s, administration of TPN + NS/NT for four days resulted in significant healing of small bowel ulcers, as indicated by decreased ulcer length . This effect of NS/NT appears to relate, in part, to increased cell p roliferation, evidenced by increased crypt length, crypt-villus ratio, mitotic index, and PCNA labeling.