Clinical Trial of Watercress in Detoxification of Environmental Toxicants and Carcinogens

西洋菜解毒环境毒物和致癌物的临床试验

• 批准号: 9755388
• 负责人: DOROTHY K HATSUKAMI
• 金额: $ 61.74万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-03 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755388
• 关键词: 2-butenal; Acetylcysteine; Acrolein; Air; Benzene; Beverages; Blood; Butanones; Carcinogens; Cells; Chemoprevention; Chemopreventive Agent; Cigarette Smoker; Clinical Research; Clinical Trials; Consumption; Crossover Design; DNA Adducts; Diet; Disease; Dose; Drug Metabolic Detoxication; Environmental Carcinogens; Excretory function; Exposure to; Food; Freeze Drying; Fruit; Glutathione; Glutathione S-Transferase; Goals; Health; Individual; Isothiocyanates; Juice; Link; Liquid Chromatography; Malignant Neoplasms; Masks; Mastication; Medicine; Metabolic; Metabolic Activation; Minnesota; Mus; Oral; Parents; Phenethyl Isothiocyanate; Placebos; Population; Powder dose form; Preparation; Prevalence; Publishing; Rattus; Saliva; Sampling; Signal Transduction; Smoker; Source; Standardization; Testing; Time; Toxic Environmental Substances; Transferase; Urine; Vegetables; Watercress; Weight; cancer chemoprevention; cancer prevention; capsule; design; dietary constituent; environmental agent; environmental stressor; exposed human population; glutathione S-transferase M1; inhibitor/antagonist; lung cancer prevention; lung carcinogenesis; non-smoker; propylene oxide; recruit; tandem mass spectrometry; tobacco specific lung carcinogen; toxicant

Clinical Trial of Watercress in Detoxification of Environmental Toxicants and Carcinogens Summary In a recently completed clinical trial, we observed that 2-phenethyl isothiocyanate (PEITC) enhanced the detoxification of the environmental toxicants and carcinogens benzene, acrolein, and crotonaldehyde, as determined by increased excretion of the corresponding mercapturic acids in the urine of subjects who took 40 mg of PEITC orally per day. The significant enhancing effect was particularly strong in individuals who were null for the glutathione-S-transferase genes GST-T1, GST-M1, or both. These exciting results, which signal enhanced detoxification of commonly occurring environmental agents in subjects exposed to PEITC, led to the design of the current clinical trial of watercress, a common vegetable which is an abundant and practically unique natural dietary source of PEITC. When watercress is chewed or otherwise macerated, PEITC is released from its parent constituent gluconasturtiin. Thus, consumption of 10 grams wet weight of watercress exposes one to about 3 mg of PEITC. We hypothesize that watercress can enhance the detoxification of multiple environmental toxicants and carcinogens, thus emerging as an inexpensive and plentiful dietary constituent with potential for prevention of cancer and possibly other environmentally linked diseases. Therefore, we propose a clinical study of watercress with the following specific aims: 1. Prepare and standardize a watercress-derived beverage or capsules and appropriate placebo for the study. Two approaches will be investigated. A). Freeze-dry the watercress to obtain a powder which will be added to a mixture of fruit juices to mask the bitter watercress flavor. Subjects will drink this juice 10 min after mixing. B). Homogenize the watercress followed by freeze drying to produce a PEITC-containing powder which will be formulated into capsules. 2. Perform a clinical trial with 350 subjects to determine the effects of the watercress preparation on detoxification of environmental toxicants and carcinogens. Using a crossover design, subjects will consume the watercress beverage or capsules, or placebo, 3 times per day for 2 weeks with a 4 week washout period between watercress and placebo treatment. The target dose will be 40 mg/day of PEITC, as in our previous study. Urine, oral cells, saliva, and blood will be collected. 3. Using liquid chromatography-tandem mass spectrometry, analyze urine samples for mercapturic acids of specific toxicants (e.g. benzene, acrolein, crotonaldehyde, propylene oxide, etc.) and for mercapturic acids generally. Our hypothesis is that detoxification of these toxicants by conjugation with glutathione, as indicated by mercapturic acid levels in urine and DNA adduct levels in oral cells, will be significantly elevated compared to placebo in subjects who consumed the watercress preparation and are null for GSTM1, GSTT1, or both. The results of this study will provide a critical test of the use of watercress as a vehicle for isothiocyanates such as PEITC which can enhance detoxification of environmental toxicants and carcinogens. If the results of the trial support our hypothesis, watercress could emerge as a cheap and convenient food for cancer prevention, consistent with the concepts of “green chemoprevention and frugal medicine.”

豆瓣菜对环境毒物和致癌物解毒的临床试验 摘要 在最近完成的一项临床试验中，我们观察到2-苯乙基异硫氰酸酯(PEITC)增强了对 环境毒物和致癌物质苯、丙烯醛和巴豆醛，通过增加排泄量来确定 每天口服40毫克PEITC的受试者尿液中相应的硫代尿酸的含量。重要的 增强效应在谷胱甘肽-S-转移酶基因Gst-T1为空的个体中尤其强烈， GST-M1或两者兼而有之。这些令人兴奋的结果，标志着对常见环境的解毒作用增强 暴露于PEITC的受试者中的药物导致了目前豆瓣菜临床试验的设计，豆瓣菜是一种常见的蔬菜 它是PEITC丰富和几乎独特的天然饮食来源。当豆瓣菜被咀嚼或其他时候 浸渍后，PEITC从其母成分葡糖胞苷中释放出来。因此，消耗10克湿重的 豆瓣菜会使人接触到大约3毫克的PEITC。我们推测豆瓣菜可以增强人体的解毒作用。 多种环境毒物和致癌物质，因此成为一种廉价和充足的饮食成分 预防癌症和可能与环境有关的其他疾病的潜力。因此，我们提出了一种临床 豆瓣菜的研究有以下具体目的： 1.为研究准备和标准化豆瓣衍生饮料或胶囊和适当的安慰剂。二 将对方法进行调查。a)。冷冻干燥豆瓣菜以获得粉末，该粉末将被添加到 果汁掩盖了豆瓣菜的苦味。受试者将在混合后10分钟喝下这种果汁。b)。使之同质化 豆瓣菜然后冷冻干燥，以产生含有PEITC的粉末，该粉末将被配制成胶囊。 2.对350名受试者进行临床试验，以确定豆瓣制剂的解毒效果 环境毒物和致癌物。使用交叉设计，受试者将饮用豆瓣菜饮料或 胶囊，或安慰剂，每天3次，持续2周，在豆瓣菜和安慰剂之间有4周的冲洗期 治疗。与我们之前的研究一样，PEITC的目标剂量将是40毫克/天。尿液、口腔细胞、唾液和血液 将会被收取。 3.用液相色谱-串联质谱法分析尿样中特定的硫代尿酸 有毒物质(如苯、丙烯醛、巴豆醛、环氧丙烷等)一般来说，对硫代尿酸也是如此。我们的 假说是这些毒物通过与谷胱甘肽结合来解毒，如硫代尿酸所示 与安慰剂相比，尿液中的水平和口腔细胞中的DNA加合物水平将显著升高 消耗了豆瓣菜制剂，并且对于GSTM1和/或GSTT1为空。 这项研究的结果将为使用豆瓣菜作为异硫氰酸酯(如PEITC)的载体提供关键测试 可增强对环境毒物和致癌物的解毒作用。如果试验结果支持我们的 假设，豆瓣菜可能成为一种廉价而方便的癌症预防食品，这与 “绿色化学预防和节俭药物。”