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营养靶向

Nutritargeting.

作者信息

Biesalski Hans Konrad, Tinz Jana

机构信息

Department of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany.

出版信息

Adv Food Nutr Res. 2008;54:179-217. doi: 10.1016/S1043-4526(07)00005-8.

Abstract

The term "nutritargeting" in analogy to the term "drug targeting" means targeting nutrients to specific "target" tissues. What is the rationale for this idea? Some tissues obviously are able to accumulate micronutrients selectively and to use them predominantly for specific functions. It has, for instance, been known for a long time that the accumulation of beta-carotene in the skin does not only provide a "golden-yellow" color but considerable antioxidative protection as well. Yet beta-carotene is only one of many antioxidants, which can be detected in the skin. Other carotenoids, for example, lutein and zeaxanthine, are preferentially found in the macula lutea, the so-called yellow spot in the eye. Here, carotenoids are subject to a metabolism typical for that tissue, which cannot be found in other tissues (e.g., formation of meso-zeaxanthine). In addition, they can specifically be absorbed into the macula. In the macula, they protect the retinal pigment epithelial cells against oxidative damage from UV light. Indeed, these two carotenoids can be protective against age-dependent macula degeneration. Another example is the tissues that are particularly rich in vitamin C, for example, the cortex of the suprarenal gland or the lens: here, vitamin C fulfills both antioxidative functions and metabolic ones as it helps in the formation of collagen structures. Approximately 40% of the body's ascorbate is stored in skeletal muscle because this tissue is relatively abundant and its cellular concentration is tenfold higher than the plasma level. Similarly, the intracellular ascorbate concentration in the brain (3 mM) greatly exceeds the level in the extracellular fluid (200-400 muM). The majority of ascorbate is stored in the astroglial cells that are capable of reducing great quantities of DHAA to ascorbate, which then becomes available for release back into the extracellular fluid. Thus, the accumulation of vitamins respectively micronutrients in single tissues is not limited to a pure storage process like the storage of vitamin A in the liver, but is often connected with important and tissue-specific metabolic functions. When single micronutrients are applied for prevention or even intervention in diseases of organs or tissues, they are usually administered in higher doses for a longer period of time. The hope is to accumulate it this way sufficiently in the tissue and to thus be able to ensure the therapeutic success. This procedure, however, leads to a "flooding" of the whole organism with micronutrients and their potential enrichment in tissues which would usually not accumulate the respective micronutrient. Thus, unexpected side effects may occur. An attractive solution to these problems in the future could be to wrap up or apply micronutrients in such a way that they can selectively reach the targeted tissue. For this approach, called "drug targeting" by pharmacologists, one could introduce the analogous expression "nutritargeting" with respect to micronutrients. For such a nutritargeting there are already a lot of examples and developments which show that it is possible to accumulate micronutrients in target tissues while simultaneously circumventing or protecting other tissues. A substantial requirement for the development of "carriers" for nutritargeting is the availability of procedures or specific carriers, which allow the selected nutrients to bypass the main barriers that are encountered when, for example, circumventing the enteral route in the targeting process. The entrance areas for such a targeting are the nasal mucosa, the oral mucosa, the cornea, the skin, or the lung. In the case of enteral application of proteins, the packaging has to resist gastric digestion and the body must be able to absorb the particles through the intestinal mucosa without hydrolyzing the proteins in order for them to reach the systemic circulation. Another field in which nutritargeting may play an important role is the diseases where either systemic absorption is not possible (e.g., malabsorption/maldigestion) or where local deficits occur, which may not or only inadequately be supplied by systemic application.

摘要

与“药物靶向”类似,“营养靶向”一词是指将营养素靶向特定的“目标”组织。这个想法的基本原理是什么?一些组织显然能够选择性地积累微量营养素,并主要将它们用于特定功能。例如,长期以来人们都知道,皮肤中积累的β-胡萝卜素不仅能赋予皮肤“金黄色”,还能提供相当程度的抗氧化保护。然而,β-胡萝卜素只是皮肤中可检测到的众多抗氧化剂之一。例如,其他类胡萝卜素,如叶黄素和玉米黄质,优先存在于黄斑(眼睛中的所谓黄斑)中。在这里,类胡萝卜素经历该组织特有的代谢过程,而这一过程在其他组织中是不存在的(例如,内消旋玉米黄质的形成)。此外,它们能够特异性地被吸收进入黄斑。在黄斑中,它们保护视网膜色素上皮细胞免受紫外线的氧化损伤。事实上,这两种类胡萝卜素可以预防与年龄相关的黄斑变性。另一个例子是富含维生素C的组织,例如肾上腺皮质或晶状体:在这里,维生素C既具有抗氧化功能,也具有代谢功能,因为它有助于胶原蛋白结构的形成。人体约40%的抗坏血酸储存在骨骼肌中,因为该组织相对丰富,其细胞内浓度比血浆水平高十倍。同样,大脑中的细胞内抗坏血酸浓度(3 mM)大大超过细胞外液中的水平(200 - 400 μM)。大部分抗坏血酸储存在星形胶质细胞中,这些细胞能够将大量的二氢抗坏血酸还原为抗坏血酸,然后抗坏血酸可释放回细胞外液中。因此,维生素或微量营养素在单个组织中的积累并不局限于像肝脏中储存维生素A那样的单纯储存过程,而是常常与重要的、组织特异性的代谢功能相关联。当使用单一微量营养素预防甚至干预器官或组织疾病时,通常会长时间给予较高剂量。人们希望通过这种方式在组织中充分积累微量营养素,从而确保治疗成功。然而,这个过程会导致整个机体被微量营养素“淹没”,并且它们可能在通常不会积累相应微量营养素的组织中富集。因此,可能会出现意想不到的副作用。未来解决这些问题的一个有吸引力的方法可能是将微量营养素包裹起来或以某种方式施用,使它们能够选择性地到达目标组织。对于药理学家称为“药物靶向”的这种方法,就微量营养素而言,可以引入类似的表述“营养靶向”。对于这种营养靶向,已经有很多例子和进展表明,有可能在目标组织中积累微量营养素,同时避开或保护其他组织。营养靶向“载体”开发的一个重要要求是要有相应的程序或特定载体,使选定的营养素能够绕过靶向过程中遇到的主要屏障,例如避开肠内途径时遇到的屏障。这种靶向的进入部位是鼻黏膜、口腔黏膜、角膜、皮肤或肺部。在通过肠道应用蛋白质的情况下,包装必须能够抵抗胃消化,并且身体必须能够通过肠黏膜吸收颗粒而不解水解蛋白质,以便它们能够进入体循环。营养靶向可能发挥重要作用的另一个领域是那些无法进行全身吸收(例如,吸收不良/消化不良)或存在局部缺乏情况的疾病,而全身应用可能无法或只能不充分地提供这些缺乏的物质。

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