QUANTITATION OF BIOMARKERS OF OXIDATIVE STRESS BY NICI-MS

通过 NICI-MS 对氧化应激生物标志物进行定量

• 批准号: 6290033
• 负责人: Kenneth Tomer
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290033
• 关键词: alcoholic beverage consumption; antioxidants; biomarker; carcinogenesis; carotenoids; clinical research; eicosanoids; human data; human tissue; lipid peroxides; mass spectrometry; nutrition aspect of cancer; nutrition related tag; oxidative stress; peroxidation; tissue /cell culture

In 1996 a workshop on Measurement of Oxidative Stress in Humans was held at NIEHS. There was a general consensus that it would be valuable to mount a study comparing various markers of oxidative stress measured from the same sample. One such marker is F2a-isoprostane which is quantitated by NICI-MS. Isoprostanes are prostaglandin-like compounds that are produced as a result of the chemical rather than enzymatic oxidation of arachidonic acid in membrane phospholipids. The isoprostanes have been shown to possess potent biological activity, and a number of studies have shown them to be accurate markers of lipid peroxidation in animal models of oxidative stress. The 8-iso-F2a- isoprostane has been the specific isomer quantified in most studies. Although there is recent evidence for some cyclooxygenase catalyzed formation of this compound, the contribution of the enzymatic pathway has appeared to be minor and primarily the result of oxidation of free lipid rather than membrane-bound lipid. The standard method for analyzing this compound is by GC/MS of the pentafluorobenzyl ester trimethylsilyl derivative under negative ion chemical ionization conditions. Our role in this study has been to establish methodology in-house for the measurement of isoprostanes in physiological samples and to provide this capability in collaboration with other groups at NIEHS/NIH. A number of other studies involving measurement of isoprostanes as an indicator of oxidative stress have also been initiated: 1)Womens Alcohol Study P. Taylor (NCI)/D. Baer, J. Judd (USDA; 2) Correlation of O.S. with mutations (T. Devereaux, LMC); identified mutations in chemically induced mouse hepatocellular adenomas and carcinomas - hypothesize mutations are the result of indirect DNA damage, possibly from O.S.; 3)Role of O.S. in lung tumor susceptibility (T. Devereaux/A. Patel)- correlate isoprostane/tumor production (in mice) as a function of age - Oxidative stress, isoprostanes, NICI-MS

1996 年，NIEHS 举办了人类氧化应激测量研讨会。人们普遍认为，开展一项研究来比较从同一样本中测量到的各种氧化应激标志物是有价值的。其中一种标记物是 F2a-异前列腺素，可通过 NICI-MS 对其进行定量。异前列腺素是类前列腺素化合物，是通过膜磷脂中花生四烯酸的化学氧化而非酶氧化而产生的。异前列腺素已被证明具有强大的生物活性，许多研究表明它们是氧化应激动物模型中脂质过氧化的准确标记物。 8-iso-F2a-异前列烷是大多数研究中定量的特定异构体。尽管最近有证据表明这种化合物的形成是由环加氧酶催化的，但酶途径的贡献似乎很小，并且主要是游离脂质而不是膜结合脂质氧化的结果。分析该化合物的标准方法是在负离子化学电离条件下对五氟苄基酯三甲基甲硅烷基衍生物进行 GC/MS 分析。我们在这项研究中的作用是建立内部测量生理样品中异前列腺素的方法，并与 NIEHS/NIH 的其他小组合作提供这种能力。许多其他涉及测量异前列烷作为氧化应激指标的研究也已启动： 1) 女性酒精研究 P. Taylor (NCI)/D。 Baer,​​ J. Judd（美国农业部；2）O.S. 的相关性有突变（T. Devereaux，LMC）；鉴定出化学诱导的小鼠肝细胞腺瘤和癌中的突变——假设突变是间接 DNA 损伤的结果，可能来自 OS； 3）操作系统的作用肺肿瘤易感性 (T. Devereaux/A. Patel) - 将异前列腺素/肿瘤产生（小鼠）与年龄的函数相关联 - 氧化应激、异前列腺素、NICI-MS