| Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. | |
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MedLine Citation:
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PMID: 16107594 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mary E Evans; Junqiang Tian; Li H Gu; Dean P Jones; Thomas R Ziegler |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: JPEN. Journal of parenteral and enteral nutrition Volume: 29 ISSN: 0148-6071 ISO Abbreviation: JPEN J Parenter Enteral Nutr Publication Date: 2005 Sep-Oct |
Date Detail:
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Created Date: 2005-08-18 Completed Date: 2006-02-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7804134 Medline TA: JPEN J Parenter Enteral Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 315-20; discussion 320-1 Citation Subset: IM |
Affiliation:
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Department of Medicine and the Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, GA 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological Animals Cell Division / drug effects, physiology Dietary Supplements Disease Models, Animal Intestinal Absorption / drug effects, physiology Intestinal Mucosa / cytology, drug effects*, growth & development, pathology Jejunum / cytology, drug effects, growth & development, pathology Male Orotic Acid / administration & dosage, pharmacology* Random Allocation Rats Rats, Sprague-Dawley Short Bowel Syndrome / diet therapy* Uracil / administration & dosage, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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F32 DK 65345/DK/NIDDK NIH HHS; R01 DK 55850/DK/NIDDK NIH HHS; R01 ES 011195/ES/NIEHS NIH HHS; R24 DK 64399/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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65-86-1/Orotic Acid; 66-22-8/Uracil |
| Comments/Corrections | |
Comment In:
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JPEN J Parenter Enteral Nutr. 2005 Sep-Oct;29(5):392-3
[PMID:
16107604
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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