Intravenous nucleosides and a nucleotide promote healing of small bowel ulcers in experimental enterocolitis

Abstract

Our aim was to evaluate the possible beneficial effect of intravenous nucleosides and a nucleotide in healing small bowel ulceration in a rat model of enterocolitis. Fourteen Lewis female rats were randomized into total parenteral nutrition (TPN, N = 7) and TPN + nucleosides and a nucleotide (NS/NT, N = 7) groups. After adaptation, two doses of indomethacin (7.5 mg/kg) were administered subcutaneously 24 hr apart to each animal in both groups. Concomitant with the first dose of indomethacin, TPN or TPN + NS/NT were infused for four days. The TPN and TPN + NS/NT were isocaloric and isonitrogenous. At the end of four days, total ulcer length in the entire small bowel was measured. The mucosa surrounding ulcers was studied by optical microscopy. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA). Ileal crypt and villus lengths were measured with an eyepiece micrometer, crypt-villus ratios were calculated, and crypt mitotic index and percentage 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 greater 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 enterocolitis, 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 proliferation, evidenced by increased crypt length, crypt-villus ratio, mitotic index, and PCNA labeling.