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Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats.
JPEN J Parenter Enteral Nutr. 2005 Sep-Oct; 29(5):315-20; discussion 320-1.JJ

Abstract

BACKGROUND

Massive small-bowel resection (SBR) increases adaptive growth of residual intestine in animal models of short-bowel syndrome (SBS). Pyrimidine nucleotides are critical for DNA and RNA synthesis, but no previous study has evaluated whether supplementation of pyrimidines or their precursors in the diet enhances adaptive gut growth after SBR. This study determined growth responses in jejunal mucosa after 7 days of dietary supplementation with uracil, or its precursor, orotate, after massive SBR in rats.

METHODS

Sprague-Dawley rats (approximately 200 g) underwent 80% jejunoileal resection (RX) or ileal transection (TX; control). Rats were pair-fed a purified (AIN-93G) powdered diet supplemented with or without 1% (wt/wt) orotate or uracil until killing at 7 days postsurgery. Defined jejunal segments were obtained for analysis of mucosal villus height (VH), crypt depth (CD), total mucosal height, bromodeoxyuridine (BrdU) incorporation, an index of cell proliferation, and full-thickness DNA and protein content as measures of intestinal adaptive growth.

RESULTS

Jejunal VH increased significantly with SBR, as expected, and orotate further stimulated this response. Jejunal CD and total mucosal height increased significantly with both orotate and uracil supplementation compared with resected animals receiving standard diet. Orotate administration also increased jejunal DNA content compared with the increase observed with SBR alone. Finally, orotate, but not uracil, supplementation increased BrdU incorporation compared with resected rats fed standard or uracil-supplemented diet after SBR.

CONCLUSIONS

Supplementation of oral diet with the pyrimidine precursor orotate and uracil stimulated adaptive jejunal growth after massive SBR in rats. Dietary orotate had more potent growth-stimulatory effects than uracil in this animal model. Dietary supplementation with orotate and uracil represents a novel nutrition approach to enhance small-bowel mucosal adaptive growth and absorptive capacity in SBS.

Authors+Show Affiliations

Department of Medicine and the Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, GA 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16107594

Citation

Evans, Mary E., et al. "Dietary Supplementation With Orotate and Uracil Increases Adaptive Growth of Jejunal Mucosa After Massive Small Bowel Resection in Rats." JPEN. Journal of Parenteral and Enteral Nutrition, vol. 29, no. 5, 2005, pp. 315-20; discussion 320-1.
Evans ME, Tian J, Gu LH, et al. Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr. 2005;29(5):315-20; discussion 320-1.
Evans, M. E., Tian, J., Gu, L. H., Jones, D. P., & Ziegler, T. R. (2005). Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. JPEN. Journal of Parenteral and Enteral Nutrition, 29(5), 315-20; discussion 320-1.
Evans ME, et al. Dietary Supplementation With Orotate and Uracil Increases Adaptive Growth of Jejunal Mucosa After Massive Small Bowel Resection in Rats. JPEN J Parenter Enteral Nutr. 2005 Sep-Oct;29(5):315-20; discussion 320-1. PubMed PMID: 16107594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. AU - Evans,Mary E, AU - Tian,Junqiang, AU - Gu,Li H, AU - Jones,Dean P, AU - Ziegler,Thomas R, PY - 2005/8/19/pubmed PY - 2006/2/28/medline PY - 2005/8/19/entrez SP - 315-20; discussion 320-1 JF - JPEN. Journal of parenteral and enteral nutrition JO - JPEN J Parenter Enteral Nutr VL - 29 IS - 5 N2 - BACKGROUND: Massive small-bowel resection (SBR) increases adaptive growth of residual intestine in animal models of short-bowel syndrome (SBS). Pyrimidine nucleotides are critical for DNA and RNA synthesis, but no previous study has evaluated whether supplementation of pyrimidines or their precursors in the diet enhances adaptive gut growth after SBR. This study determined growth responses in jejunal mucosa after 7 days of dietary supplementation with uracil, or its precursor, orotate, after massive SBR in rats. METHODS: Sprague-Dawley rats (approximately 200 g) underwent 80% jejunoileal resection (RX) or ileal transection (TX; control). Rats were pair-fed a purified (AIN-93G) powdered diet supplemented with or without 1% (wt/wt) orotate or uracil until killing at 7 days postsurgery. Defined jejunal segments were obtained for analysis of mucosal villus height (VH), crypt depth (CD), total mucosal height, bromodeoxyuridine (BrdU) incorporation, an index of cell proliferation, and full-thickness DNA and protein content as measures of intestinal adaptive growth. RESULTS: Jejunal VH increased significantly with SBR, as expected, and orotate further stimulated this response. Jejunal CD and total mucosal height increased significantly with both orotate and uracil supplementation compared with resected animals receiving standard diet. Orotate administration also increased jejunal DNA content compared with the increase observed with SBR alone. Finally, orotate, but not uracil, supplementation increased BrdU incorporation compared with resected rats fed standard or uracil-supplemented diet after SBR. CONCLUSIONS: Supplementation of oral diet with the pyrimidine precursor orotate and uracil stimulated adaptive jejunal growth after massive SBR in rats. Dietary orotate had more potent growth-stimulatory effects than uracil in this animal model. Dietary supplementation with orotate and uracil represents a novel nutrition approach to enhance small-bowel mucosal adaptive growth and absorptive capacity in SBS. SN - 0148-6071 UR - https://www.unboundmedicine.com/medline/citation/16107594/Dietary_supplementation_with_orotate_and_uracil_increases_adaptive_growth_of_jejunal_mucosa_after_massive_small_bowel_resection_in_rats_ L2 - https://doi.org/10.1177/0148607105029005315 DB - PRIME DP - Unbound Medicine ER -