Dietary Nucleotides Augment Dextran Sulfate Sodium-Induced Distal Colitis in Rats

Sukumar, Prabha; Loo, A. A. J. van de; Adolphe, Renald; Nandi, Jyotirmoy; Oler, Albert; Levine, Robert A.

doi:10.1093/jn/129.7.1377

Cited by 9 publications

(6 citation statements)

References 26 publications

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“…Similarly, a study in rats on the effect of dietary supplementation with a nucleoside/NT mixture showed that it exacerbated the injury associated with dextran sodium sulphate induced colitis. 16 Further studies on the potential benefits (and risks) of NT supplementation, therefore, appear justified. …”

Section: Discussionmentioning

confidence: 99%

Gastroprotective effects of oral nucleotide administration

Belo

Marchbank²,

Fitzgerald³

et al. 2006

Gut

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Background and aims: Nucleotides form the building blocks of DNA and are marketed as dietary supplements, alone or in combination with other ingredients, to promote general health. However, there has been only limited scientific study regarding the true biological activity of orally administered nucleotides. We therefore tested their efficacy in a variety of models of epithelial injury and repair. Methods: Effects on proliferation ([ 3 H] thymidine incorporation) and restitution (cell migration of wounded monolayers) were analysed using HT29 and IEC6 cells. The ability of a nucleotide mixture to influence gastric injury when administered orally and subcutaneously was analysed using a rat indomethacin (20 mg/kg) restraint model. Results: In both cell lines, cell migration was increased by approximately twofold when added at 1 mg/ml (p,0.01); synergistic responses were seen when a mixture of nucleotides was used. Cell proliferation was stimulated by adenosine monophosphate (AMP) in HT29, but not in IEC6, cells. Gastric injury was reduced by approximately 60% when gavaged at 4-16 mg/ml (p,0.05), concentrations similar to those likely to be found in consumers taking nucleotide supplements. Systemic administration of nucleotides was unhelpful. Conclusions: Nucleotides possess biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies on their potential benefits (and risks) appear justified. N atural medicinal products have been used for millennia for the treatment of multiple ailments. Although many have been superseded by conventional pharmaceutical approaches, there is currently a resurgence of interest in the use of natural bioactive products by the general public, with many healthy subjects and patients taking them for the prevention and treatment of multiple conditions, including gastrointestinal disorders and postoperative recovery. Unfortunately, current evidence of the scientific validity of many of these traditional and commercial compounds is severely limited.Nucleosides and nucleotides (NTs) serve as building blocks for RNA and DNA synthesis for cells. Cell turnover is very rapid in the gut and requires considerable amounts of NTs. The intestine can synthesise NTs from amino acids and other precursors but de novo NTs synthesis may be limited and the gut may also be dependent on exogenous supplies of NTs. NTs are currently sold in pure individual form (particularly adenosine based), as NT mixtures, or as part of multiple ingredients in dietary supplements in health food shops. Multiple claims for these products have been made, including improving gastrointestinal and liver health, strengthening the immune system, promoting tissue renewal and wound healing, and benefiting athletic performance. The strength of the data supporting these claims are however limited.We have therefore perfor...

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Section: Discussionmentioning

confidence: 99%

Gastroprotective effects of oral nucleotide administration

Belo

Marchbank²,

Fitzgerald³

et al. 2006

Gut

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“…Inflammation was assessed on the basis of criteria described in Table 1 (36,37). The final number was the sum of the diarrhea score, the visible fecal blood score, and the examination of the anus.…”

Section: Methodsmentioning

confidence: 99%

Hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2A

Schwartz¹,

Abolhassani²,

Pooya³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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There are several reports suggesting hyperosmotic contents in the feces of patients suffering from inflammatory bowel disease (IBD). Previous works have documented that hyperosmolarity can cause inflammation attributable to methylation of the catalytic subunit of protein phosphatase 2A (PP2A) and subsequent NF-kappaB activation resulting in cytokine secretion. In this study, we demonstrate that dextran sulfate sodium (DSS) induces colitis due to hyperosmolarity and subsequent PP2A activation. Mice were randomized and fed with increased concentrations of DSS (0 mOsm, 175 mOsm, 300 mOsm, and 627 mOsm) for a duration of 3 wk or with hyperosmotic concentrations of DSS (627 mOsm) or mannitol (450 mOsm) for a duration of 12 wk. Long-term oral administration of hyposmotic DSS or mannitol had no demonstrable effect. Hyperosmotic DSS or mannitol produced a significant increase in colonic inflammation, as well as an increase in the weight of sacral lymph nodes and in serum amyloid A protein levels. Similar results were obtained through the ingestion of comparable osmolarities of mannitol. Hyperosmolarity induces the methylation of PP2A, nuclear p65 NF-kappaB activation. and cytokine secretion. The rectal instillation of okadaic acid, a well-known PP2A inhibitor, reverses the IBD. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reverse the effect of hyperosmotic DSS. The present study strongly suggests that DSS-induced chronic colitis is a consequence of the methylation of PP2Ac induced by hyperosmolarity.

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“…Indomethacin‐induced enteritis, a condition that shares clinical, histological, and pathophysiological characteristics with Crohn's disease, exhibited significant acceleration in ulcer healing and significant decreases in total ulcer length and number in the small intestine after exogenous nucleotide supplementation 62 , 63 . However, one of these same labs found that when dextran sulfate sodium salt (DSS) was used to induce distal colitis in rats, the nucleotide‐supplemented group showed more inflammation than the nucleotide‐free group, which achieved faster healing of the colitis 64 . In another model of colonic damage that used trinitrobenzene sulfonic acid (TNBS) to induce colitis, the control group also had improved recovery as compared with the nucleoside‐nucleotide‐supplemented group.…”

Section: Representative Animal Studies With Nucleotidesmentioning

confidence: 99%

The Role of Nucleotides in the Immune and Gastrointestinal Systems

2012

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Nucleotides are low molecular weight biological molecules key to biochemical processes. Sources include de novo synthesis, recovery via salvage mechanisms, and dietary intakes. Although endogenous production serves as the main nucleotide source, evidence suggests that exogenous sources are essential to immune competence, intestinal development, and recovery. Dietary nucleotides serve a marked role in rapidly proliferating cells where they are necessary for optimal function. Accordingly, dietary nucleotides are deemed conditionally essential in the presence of various physiological stresses, including growth and development, recovery from injury, infection, and certain disease states. Clinical studies that evaluated nutrition formulations of nucleotides in combination with other specific nutrient substances demonstrated improved clinical outcomes in patients characterized as critically ill, injured, immune suppressed, or with chronic gastrointestinal conditions. However, conclusions regarding specific benefits of nucleotides are limited. Scientific substantiation of nucleotide supplementation in infant formula has been reported to improve the maturation and development of the intestinal tract as well as immune function. All medical nutrition products except for one immune-modulating formulation are devoid of nucleotides. In an effort to build on this, the current review presents the data to support potential clinical applications for nucleotides in enteral nutrition that may contribute to improved outcomes in physiologically stressed patients.

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Dietary Nucleotides Augment Dextran Sulfate Sodium-Induced Distal Colitis in Rats

Cited by 9 publications

References 26 publications

Gastroprotective effects of oral nucleotide administration

Gastroprotective effects of oral nucleotide administration

Hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2A

The Role of Nucleotides in the Immune and Gastrointestinal Systems

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