Biomarkers Of Oxidative Stress Study

该项目的最终目标是确定啮齿动物、非人类灵长类动物和人类氧化损伤的可测量、敏感和特定的生物标志物。对四氯化碳给药大鼠进行了初步研究，比较和评价了评估体内氧化应激状态的不同方法。臭氧暴露于大鼠被用作氧化应激的第二个模型。向世界各地的20名调查人员提供了在三个时间点和三个剂量暴露期间从大鼠身上采集的足够的生物标本（血液和尿液）。来自NIEHS外部20个实验室和NIEHS内部5个实验室的研究人员对每个样品进行了一系列氧化应激测量——异prostanes、蛋白质氧化、蛋白质羰基、o-酪氨酸、间酪氨酸、硝基酪氨酸、二酪氨酸、氯酪氨酸、8-羟基脱氧鸟苷（8-OHdG）、单细胞凝胶(SCG)/comet测定、GSH/GSSG、硫代巴比妥酸活性物质（TBARS）、脂质过氧化醛、脂质氢过氧化物、自由基生成和抗氧化剂。目前，四氯化碳中毒模型的结果已经完成。统计分析显示，四氯化碳中毒使血浆和尿液中异前列腺素和丙二醛的生成呈时间和剂量依赖性增加。因此，这些标志物的变化是氧化应激的指示。血浆抗氧化剂不能作为急性四氯化碳中毒模型中氧化应激的标志物。从接触臭氧的动物身上收集数据仍在进行中。

The ultimate goal of the project is to determine measurable, sensitive, and specific biomarkers for oxidative damage in rodents, nonhuman primates and humans. An initial study of carbon tetrachloride-dosed rats was conducted to compare and evaluate different assays in the assessment of oxidant stress status in vivo. Ozone exposure to rats was used as a second model of oxidative stress. Sufficient samples of biological specimens (blood and urine) taken from rats over three time points and three doses of exposure were provided to 20 investigators worldwide. A battery of oxidative stress measurements- isoprostanes, protein oxidation, protein carbonyls, o-tyrosine, m-tyrosine, nitrotyrosine, dityrosine, chlorotyrosine, 8-hydroxydeoxyguanosine (8-OHdG), Single Cell Gel (SCG)/comet assay, GSH/GSSG, thiobarbituric acid reactive substances (TBARS), aldehydes from lipid peroxidation, lipid hydroperoxides, free radical generation and antioxidants were run on each sample by investigators from 20 labs outside NIEHS and 5 labs from NIEHS. At present, results from the model of carbon tetrachloride poisoning have been completed. As shown by the statistical analyses, carbon tetrachloride poisoning increased the generation of isoprostanes and MDA in plasma and urine in time- and dose-dependent manners. Therefore, changes in these markers are indicative of oxidative stress. It was also found that plasma antioxidants can not be used as markers of oxidative stress in a model of acute carbon tetrachloride poisoning. Collecting data from the ozone exposed animals is still in progress.