A Total Parenteral Nutrition Solution Supplemented with a Nucleoside and Nucleotide Mixture Sustains Intestinal Integrity, but Does Not Stimulate Intestinal Function after Massive Bowel Resection in Rats

Abstract

The effects of supplementing a total parenteral nutrition solution with a nucleoside and nucleotide mixture on mucosal adaptive processes after massive bowel resection were studied. Male Wistar rats (n=30) underwent 80% small intestine resection, were randomized into two groups and received either standard total parenteral nutrition (TPN) or TPN supplemented with a nucleoside and nucleotide mixture (2.5 mL.kg-1.d-1). An additional five rats, fed a nonpurified diet and not resected, were used as controls. After 4 or 7 d, rats were killed and samples were collected for mucosal indices and intestinal enzymatic activities (disaccharidases and diamine oxidase). After massive small bowel resection and TPN, residual jejunal mucosal wet weights, villus heights, protein and RNA contents on d 4 and 7, and total wet weights and DNA contents on d 7 were significantly lower than in the control group. Administration of the nucleoside and nucleotide mixture resulted in significantly higher residual jejunal total and mucosal weights, proteins, DNA, RNA contents, and the ratio of proliferating cell nuclear antigen positive cells per crypt than did the standard TPN solution on d 7. However, disaccharidase and diamine oxidase activities were not affected by supplementation with the nucleoside and nucleotide mixture. Our data suggest the supplementation of a nucleoside and nucleotide mixture to a TPN solution can attenuate the initial mucosal atrophy and improve intestinal cell turnover after massive bowel resection, but the supplementation has little effect on enterocyte enzymatic activities.

Dietary Supplementation With Orotate and Uracil Increases Adaptive Growth of Jejunal Mucosa After Massive Small Bowel Resection in Rats

“…31,32,37,40 In the present study, we show for the first time that dietary supplementation with the pyrimidine precursor orotate and its downstream nucleic acid uracil are associated with increased jejunal adaptive growth after massive SBR in rats. The adaptive increase in jejunal growth indices with dietary orotate and uracil is quantitatively similar to that observed with peptide growth factors in similar models of SBS in rats (eg, glucagon-like peptide-2 and growth hormone).…”

“…The adaptive increase in jejunal growth indices with dietary orotate and uracil is quantitatively similar to that observed with peptide growth factors in similar models of SBS in rats (eg, glucagon-like peptide-2 and growth hormone). 24 Previous studies by Iijima et al 37,40 in the 80% SBR rat model found that supplementation of PN with a nucleoside and nucleotide mixture increased jejunal total and mucosal wet weight, protein, DNA, RNA, and cell proliferation and ileal mucosal wet weight, protein content and villus height after 7 days compared with unsupplemented PN but had no effect on disaccharidase activity. However, to our knowledge, no previous studies have investigated the effects of enteral dietary supplementation with either nucleic acids or pyrimidines on intestinal adaptation after massive intestinal resection.…”

“…35,36 In a rat model of SBS, IV administration of nucleotide mixtures in PN increased jejunal villus height and cell proliferation and decreased gut permeability to sugar markers. 37 However, the effects of enteral administration of orotate or specific nucleotides on gut adaptation after resection have not been evaluated. The aim of this study was to investigate the effect of dietary supplementation with the pyrimidine, uracil, or its precursor, orotate, on indices of jejunal adaptive growth after 80% jejunal-ileal resection in rats.…”

The Role of Nucleotides in the Immune and Gastrointestinal Systems

“…These findings suggested that nucleotides influence intestinal growth, protection, and maintenance in small bowel transplantation. In further support, rats maintained on standard PN supplemented with a nucleoside‐nucleotide mixture after massive bowel resection demonstrated attenuated initial mucosal atrophy and improved intestinal cell turnover 56 …”

Metabolic consequences of patients with gastrointestinal fistulas

“…On the other hand, the current generations of enteral diets are superior to currently available parenteral solutions because the enteral formulations can provide arginine, glutamine, omega-3-containing fish oils, nucleosides, and nucleotides [28,33]. The advocates of these nutrients have shown beneficial physiologic effects in supporting alimentary tract mucosal growth and function, and general immunocompetence, which are important in the management of critically ill patients in whom the intestinal mucosal barrier may be compromised [34].…”