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）：富含类胡萝卜素的西红柿和许多西红柿衍生产品在过去十年中已广泛销售，用于促进健康和预防疾病。然而，争议仍然存在，很大程度上是因为人们对番茄主要类胡萝卜素番茄红素 (LYC)、八氢番茄红素 (PE) 和六氢番茄红素 (PF) 的生物利用度、代谢和作用机制知之甚少。该拨款申请描述了一种新型研究工具的表征和实施，该工具将极大地提高我们追踪番茄类胡萝卜素代谢物吸收的能力。本申请中描述和测试的新技术基于生产 13C 标记的 LYC、PE 和 PF 并在人体中进行测试。这些富含 13C 的类胡萝卜素将用于交叉喂养研究，旨在更精确地定义和比较男性和女性如何吸收和代谢番茄类胡萝卜素。具体目标1：利用体外番茄细胞悬浮培养技术生产纯13C-八氢番茄红素（PE）、13C-六氢番茄红素（PF）和13C-番茄红素（LYC）。我们将首次应用番茄细胞悬浮培养来可靠生产高度纯化的非放射性富含 13C 的番茄类胡萝卜素 PE、PF 和 LYC，用于人体新的生物利用度和代谢研究。具体目标#2：使用 13C -PE、13C -PF 和 13C-LYC 比较和定义男性和女性番茄衍生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 来表征健康成年男性 (n=12) 和女性 (n=12) 中这些番茄类胡萝卜素的吸收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 来鉴定人体中番茄衍生类胡萝卜素随时间的代谢物。对人类中番茄衍生的类胡萝卜素代谢的认识和理解充其量只是推测，而且在降解途径和潜在生物活性化合物的产生方面基本上不存在。示踪剂标记将使我们能够使用 HPLC-MS/MS 检查口服母体化合物向代谢物的转化，这些代谢物是生物活化途径或分解代谢/降解途径的特征。意义。只有通过开发新工具来检查消化、吸收、生物利用度、组织分布以及全身与靶组织代谢，我们才能了解 LYC、PE 和 PF 对人类健康的作用机制。本提案针对国家补充和替代医学中心 (NCCAM)、NCI、国家老龄化研究所题为“人类补充和替代医学 (CAM) 研究探索性/发展资助”的计划公告 PAR-08-135（ NIA）和膳食补充剂办公室（ODS）。公共健康相关性：该提案描述了新技术的研究，这些新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、六氢番茄红素和八氢番茄红素在促进人类健康和预防疾病方面的作用机制。