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.”

西洋菜解毒环境毒物和致癌物的临床试验 概括 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 通过排泄增加确定环境毒物和致癌物苯、丙烯醛和巴豆醛 每天口服 40 毫克 PEITC 的受试者尿液中相应硫醇酸的含量。显着的 对于谷胱甘肽-S-转移酶基因 GST-T1 无效的个体，增强作用尤其强烈， GST-M1，或两者兼而有之。这些令人兴奋的结果表明常见环境中常见物质的解毒能力增强 暴露于 PEITC 的受试者中的药剂，导致了目前对豆瓣菜（一种常见蔬菜）的临床试验的设计 这是 PEITC 丰富且独特的天然膳食来源。当豆瓣菜被咀嚼或以其他方式时 浸渍后，PEITC 从其母体成分葡糖苷中释放出来。因此，消耗 10 克湿重 豆瓣菜暴露 1 至约 3 毫克 PEITC。我们假设豆瓣菜可以增强解毒能力 多种环境毒物和致癌物，因此成为一种廉价且丰富的膳食成分 预防癌症和其他可能与环境有关的疾病的潜力。因此，我们提出临床 对豆瓣菜的研究具有以下具体目标： 1. 为研究准备并标准化豆瓣菜饮料或胶囊以及适当的安慰剂。二 将研究方法。一个）。将豆瓣菜冷冻干燥以获得粉末，将其添加到混合物中 果汁掩盖西洋菜的苦味。受试者将在混合后 10 分钟饮用该果汁。 B）。均质化 西洋菜，然后冷冻干燥，生产出含有 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，以确定豆瓣菜制剂对解毒的效果 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，豆瓣菜和安慰剂之间有 4 周的冲洗期 治疗。正如我们之前的研究一样，PEITC 的目标剂量为 40 毫克/天。尿液、口腔细胞、唾液和血液 将被收集。 3. 使用液相色谱-串联质谱法，分析尿样中特定的硫醇酸 有毒物质（例如苯、丙烯醛、巴豆醛、环氧丙烷等）和硫醇酸。我们的 假设是通过与谷胱甘肽结合来解毒这些毒物，如硫醇酸所示 与安慰剂相比，受试者的尿液中的水平和口腔细胞中的 DNA 加合物水平将显着升高 消耗了豆瓣菜制剂，并且 GSTM1、GSTT1 或两者均无效。 这项研究的结果将为使用豆瓣菜作为异硫氰酸盐（例如 PEITC）的载体提供关键测试 可以增强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且方便的癌症预防食品，这与以下概念一致： “绿色化学预防和节俭医疗。”