Novel 13-C Tomato Carotenoids for Absorption and Metabolism Studies in Humans

用于人体吸收和代谢研究的新型 13-C 番茄类胡萝卜素

• 批准号: 7897381
• 负责人: STEVEN K CLINTON
• 金额: $ 20.12万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897381
• 关键词: Address; Adult; American; Animal Model; Appearance; Applications Grants; Biodistribution; Biological Availability; Blood specimen; Cardiovascular Diseases; Carotene; Carotenoids; Case-Control Studies; Cell Culture Techniques; Cells; Characteristics; Chronic; Clinical Research; Clinical Trials; Complementary and alternative medicine; Consumption; Crossover Design; Data; Degradation Pathway; Development; Diet; Digestion; Dose; Drug or chemical Tissue Distribution; Epidemiologic Studies; Epidemiology; Exploratory/Developmental Grant; Figs - dietary; Food; Food Labeling; Foundations; Funding; Gender; Genetic Crossing Over; Grant; Health; Health Promotion; Human; Hybrids; In Vitro; Individual; Institutes; Intake; International; Intervention; Intervention Trial; Joints; Kinetics; Knowledge; Label; Laboratories; Laboratory Research; Literature; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Marketing; Mass Spectrum Analysis; Metabolic; Metabolism; Methodology; Methods; Molecular; Monitor; NIH Program Announcements; National Center for Complementary and Alternative Medicine; National Institute on Aging; Nutrient; Nutritionist; Ovarian; Parents; Pathway interactions; Pharmacologic Substance; Pharmacology; Phase; Phytochemical; Plants; Plasma; Play; Policy Maker; Population; Prevention; Prevention therapy; Production; Property; Prostate; Publications; Publishing; Qualifying; Radioactive; Radiolabeled; Randomized; Relative (related person); Reporting; Research; Research Design; Research Project Grants; Risk; Rodent; Role; Scientist; Series; Stable Isotope Labeling; Stomach; Sucrose; Suspension Culture; Techniques; Technology; Testing; Time; Tissues; Tomatoes; Tracer; Vitamin A; Vitamin A Deficiency; Woman; Work; absorption; anticancer research; base; cellular targeting; cohort; desaturase; design; dietary supplements; disorder prevention; experience; fascinate; feeding; improved; inhibitor/antagonist; interest; lycopene; men; metabolic abnormality assessment; new technology; novel; novel strategies; phytoene; phytofluene; pilot trial; prostate cancer prevention; prostate carcinogenesis; protective effect; public health relevance; radiotracer; stable isotope; tool; uptake

DESCRIPTION (provided by applicant): Carotenoid-rich tomatoes and many products derived from tomatoes have been extensively marketed in the last decade for health promotion and disease prevention. Yet, controversy abounds, in large part because so little it known about the bioavailability, metabolism and mechanisms of action of the major tomato carotenoids lycopene (LYC), phytoene (PE) and phytofluene (PF). This grant application describes the characterization and implementation of a novel research tool that will dramatically improve our ability to trace the absorption of metabolites derived from the tomato carotenoids. The new technology, described and tested in this application, is based upon producing 13C labeled LYC, PE, and PF and testing them in humans. These 13C-enriched carotenoids will be used in a cross-over feeding study designed to more precisely define and compare how tomato carotenoids are absorbed and metabolized in men and women. Specific Aim 1: To produce pure 13C- phytoene (PE), 13C- phytofluene (PF) and 13C-lycopene (LYC) by utilizing in vitro tomato cell suspension culture technology. For the first time, we will apply tomato cell suspension culture for the reliable production of highly purified non-radioactive 13C-rich tomato carotenoids PE, PF, and LYC for novel bioavailability and metabolism studies in humans. Specific Aim #2: To compare and define kinetics of absorption and relative bioavailability of tomato-derived carotenoids in men and women using 13C -PE, 13C -PF, and 13C-LYC. We will use 13C-PE, 13C-PF, and 13C-LYC for characterization of uptake kinetics and relative bioavailability of these tomato carotenoids in healthy adult men (n=12) and women (n=12). Specific Aim 3: To identify metabolites of tomato-derived carotenoids in humans over time by employing 13C-PE, 13C-PF, or 13C-LYC. Knowledge and understanding of tomato-derived carotenoid metabolism in humans is speculative at best and essentially nonexistent with regards to both degradation pathways, and production of potentially bioactive compounds. Tracer labeling will allow us to examine the conversion of the orally administered parent compound to metabolites that are characteristic of bioactivation pathways or catabolic/degradation pathways using HPLC-MS/MS. Significance. Only through the development of novel tools to examine the digestion, absorption, bioavailability, tissue distribution, and systemic vs. target tissue metabolism will we be able to understand the mechanisms of action for LYC, PE, and PF in regards to human health. This proposal targets the Program Announcement PAR-08-135 entitled "Exploratory/Developmental Grant for Complementary and Alternative Medicine (CAM) Studies of Humans" of The National Center for Complementary and Alternative Medicine (NCCAM), NCI, the National Institute on Aging (NIA), and the Office of Dietary Supplements (ODS). PUBLIC HEALTH RELEVANCE: This proposal describes studies that characterize new techniques that will help us understand the absorption and metabolism of the major tomato carotenoids. These studies may help us defined the mechanisms of action for lycopene, phytofluene, and phytoene with regards to human health promotion and disease prevention.

描述(申请人提供)：富含类胡萝卜素的西红柿和许多从西红柿中提取的产品在过去十年中被广泛推向市场，用于促进健康和预防疾病。然而，争议很大程度上是因为人们对番茄中主要的类胡萝卜素番茄红素(Lyc)、植烯(PE)和植氟烯(PF)的生物利用度、代谢和作用机制知之甚少。这项拨款申请描述了一种新的研究工具的特征和实施，该工具将极大地提高我们追踪来自番茄类胡萝卜素的代谢物的吸收的能力。在本申请中描述和测试的这项新技术是基于生产标记为lyc、PE和PF的13C并在人体上测试它们。这些富含13C的类胡萝卜素将用于交叉喂养研究，旨在更准确地定义和比较男性和女性对番茄类胡萝卜素的吸收和代谢。具体目标1：利用番茄细胞体外悬浮培养技术，生产高纯度的13C-植烯(PE)、13C-植茂(PF)和13C-番茄红素(LYC)。我们将首次将番茄细胞悬浮培养用于生产高纯度、非放射性的富含13C的番茄类胡萝卜素PE、PF和LYC，用于人类新的生物利用度和新陈代谢研究。具体目标#2：使用13C-PE、13C-PF和13C-lyC比较和确定番茄类胡萝卜素在男性和女性中的吸收动力学和相对生物利用度。我们将使用13C-PE、13C-PF和13C-lyC来表征这些番茄类胡萝卜素在健康成年男性(n=12)和女性(n=12)中的摄取动力学和相对生物利用度。具体目标3：通过使用13C-PE、13C-PF或13C-lyC来鉴定番茄类胡萝卜素在人体内随时间的代谢物。人类对番茄类胡萝卜素代谢的了解充其量是推测的，在降解途径和潜在生物活性化合物的产生方面基本上是不存在的。示踪剂标记将使我们能够使用高效液相-质谱仪/质谱仪检查口服母体化合物转化为具有生物激活途径或分解代谢/降解途径特征的代谢物的情况。只有通过开发新的工具来检测LYC、PE和PF的消化、吸收、生物利用度、组织分布和系统与靶组织代谢，我们才能了解LYC、PE和PF与人类健康相关的作用机制。这项建议针对的是国家补充和替代医学中心(NCCAM)、NCI、国家老龄研究所(NIA)和膳食补充剂办公室(Ods)的项目公告PAR-08-135，题为“人类补充和替代医学(CAM)研究的探索/发展资助”。 与公共健康相关：这项建议描述了新技术的特征，这些技术将帮助我们了解主要番茄类胡萝卜素的吸收和代谢。这些研究可能有助于我们确定番茄红素、植氟烯和植烯在促进人类健康和预防疾病方面的作用机制。