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白藜芦醇在人类癌症化学预防中的应用——选择“合适”的剂量。

Resveratrol in human cancer chemoprevention--choosing the 'right' dose.

机构信息

Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.

出版信息

Mol Nutr Food Res. 2012 Jan;56(1):7-13. doi: 10.1002/mnfr.201100400. Epub 2011 Oct 7.

Abstract

There is now robust preclinical evidence to suggest that resveratrol possesses cancer chemopreventive properties. A series of clinical pilot studies has provided insights into its pharmacokinetics, and data on its human antineoplastic pharmacodynamics start to emerge. It is likely that resveratrol will be developed further in the clinic as a putative cancer chemopreventive agent. The question that remains unresolved is: What is the most suitable dose of resveratrol for effective cancer preventive intervention? Mechanistic studies in cells in vitro have almost invariably used concentrations of resveratrol in the 10(-5) to 10(-4)  M range, which is much higher than those which can be achieved in the human biophase after consumption of doses up to 1 g. Many of the preclinical efficacy studies in rodent models of carcinogenesis have employed doses which are dramatically above those which can be ingested with the diet. New experimental paradigms need to be used to obtain information on pharmacological changes elicited by resveratrol when present at very low concentrations or when administered at dietary-relevant doses.

摘要

现在有大量的临床前证据表明白藜芦醇具有抗癌化学预防特性。一系列临床初步研究提供了其药代动力学的见解,并且关于其人类抗肿瘤药效学的数据开始出现。白藜芦醇很可能会在临床上进一步开发作为一种潜在的癌症化学预防剂。仍然悬而未决的问题是:有效预防癌症干预的白藜芦醇最合适剂量是多少?体外细胞的机制研究几乎都使用了 10(-5)至 10(-4)M 范围内的白藜芦醇浓度,这远远高于在人类生物相中摄入高达 1g 剂量后所能达到的浓度。许多致癌发生的啮齿动物模型中的临床前疗效研究都使用了远远超过饮食摄入剂量的剂量。需要使用新的实验范例来获取关于在非常低浓度存在或在相关饮食剂量下给予时白藜芦醇引起的药理变化的信息。

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