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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：在过去的十年中，用于促进健康和疾病的预防，富含类胡萝卜素的西红柿和许多来自西红柿的产品已广泛销售。然而，有争议的争议在很大程度上是因为对主要番茄类胡萝卜素番茄红素（LYC），植物（PE）和植物（PF）的生物利用度，代谢和作用机制知之甚少。该赠款应用描述了一种新颖的研究工具的表征和实施，该工具将显着提高我们追踪源自西红柿类胡萝卜素的代谢产物吸收的能力。在本应用程序中描述和测试的新技术基于生产13C标记的LYC，PE和PF并在人类中进行测试。这些富含13C的类胡萝卜素将用于一项交叉喂养研究中，旨在更精确地定义和比较男性和女性中番茄类胡萝卜素的吸收和代谢。特定目标1：通过利用体外番茄细胞悬浮培养技术生产纯13c-植物（PE），13c-植物（PF）和13C-糖烯（LYC）。我们将第一次将番茄细胞悬浮培养物应用于可靠的高度纯化的非放射性13C富含13C的番茄类胡萝卜素PE，PF和LYC，以在人类中进行新颖的生物利用度和代谢研究。特定目的2：使用13C -PE，13C -PF和13C -LYC比较和定义番茄衍生的类胡萝卜素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来表征摄取动力学和这些番茄类胡萝卜素在健康的成年男性（n = 12）和女性（n = 12）中的这些番茄类胡萝卜素的相对生物利用度。特定目的3：通过使用13C-PE，13C-PF或13C-LYC，随着时间的推移，鉴定人类中番茄衍生的类胡萝卜素的代谢产物。关于人类番茄衍生的类胡萝卜素代谢的知识和理解充其量是推测性的，对于两种降解途径和产生潜在的生物活性化合物的产生，本质上是不存在的。示踪剂标记将使我们能够使用HPLC-MS/MS检查口服的母体化合物向代谢产物的转化或分解代谢途径或分解代谢/降解途径的转化。意义。只有通过开发新的工具来检查消化，吸收，生物利用度，组织分布以及全身性组织与目标组织代谢，我们将能够了解LYC，PE和PF的作用机制，以了解人类健康。该提案针对计划公告，标题为“ 08-135”，标题为“探索/发展赠款，用于人类的补充和替代医学研究（CAM）研究”国家补充和替代医学中心（NCCAM），NCI，美国国家衰老研究所（NIA）（NIA）以及饮食补充剂办公室（ODS）。公共卫生相关性：该提案描述了特征的研究，这些研究将有助于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定义番茄红素，植物氟苯和植物方面的作用机制。