Belo A, Marchbank T, Fitzgerald A, Ghosh S, Playford R J
Department of Gastroenterology, Imperial College Faculty of Medicine, Hammersmith Hospital, Ducane Rd, London W12 0NN, UK.
Gut. 2006 Feb;55(2):165-71. doi: 10.1136/gut.2005.076752. Epub 2005 Aug 9.
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.
Effects on proliferation ([3H] 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.
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.
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.
核苷酸是DNA的组成成分,作为膳食补充剂单独或与其他成分联合销售,以促进整体健康。然而,关于口服核苷酸的真正生物活性的科学研究有限。因此,我们在多种上皮损伤和修复模型中测试了它们的功效。
使用HT29和IEC6细胞分析对增殖([3H]胸苷掺入)和修复(损伤单层细胞的迁移)的影响。使用大鼠吲哚美辛(20mg/kg)束缚模型分析口服和皮下给予核苷酸混合物对胃损伤的影响。
在两种细胞系中,当以1mg/ml添加时,细胞迁移增加约两倍(p<0.01);使用核苷酸混合物时观察到协同反应。在HT29细胞中,单磷酸腺苷(AMP)刺激细胞增殖,但在IEC6细胞中则不然。当以4-16mg/ml灌胃时,胃损伤减少约60%(p<0.05),该浓度与服用核苷酸补充剂的消费者体内可能发现的浓度相似。全身给予核苷酸没有帮助。
在多种损伤和修复模型中分析时,核苷酸具有生物活性,可为预防和治疗非甾体抗炎药及其他肠道溃疡性疾病的有害影响提供一种新的廉价方法。对其潜在益处(和风险)进行进一步研究似乎是合理的。