Biomarkers Of Oxidative Stress Study

氧化应激研究的生物标志物

• 批准号: 7968022
• 负责人: RONALD P MASON
• 金额: $ 22.06万
• 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/7968022
• 关键词: Acute; Animal Model; Antioxidants; Ascorbic Acid; Biological Markers; Biology; Comparative Study; DNA strand break; Dermal; Dose; Experimental Animal Model; Exposure to; Free Radicals; Glutathione; Glutathione Disulfide; Immunoassay; Isoprostanes; Laboratories; Leadership; Lipid Peroxidation; Lipid Peroxides; Malondialdehyde; Measurement; Measures; Mediating; Medicine; Methionine; Miniature Swine; Modeling; National Institute of Environmental Health Sciences; Oxidative Stress; Ozone; Pattern; Plasma; Proteins; Publications; Publishing; Rattus; Reporting; Research; Research Personnel; Rodent; Sampling; Sensitivity and Specificity; Techniques; Testing; Time; Tyrosine; Ubiquinone; Uric Acid; Urine; alpha Tocopherol; cumene; cumene hydroperoxide; insight; oxidation; ozone exposure; urinary

We now have new findings from measurement of oxidative stress in two additional experimental animal models of oxidative stress: 90-day cumene hydroperoxde dermal exposure and LPS treatment of minipigs. The time and dose-dependent effects of these oxidative insults on plasma and urine concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA) and isoprostanes were investigated with both old and new techniques. Measures of oxidative products of proteins (protein carbonyls, methionine sulfoxidation, and tyrosine oxidation products) and of DNA (strand breaks, 8-OHdG, and M1G) were carried out as well. In addition, the time- and dose-dependent effects of the two exposures on plasma levels of alpha-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid and total antioxidant capacity were investigated to determine whether the oxidative effects of diverse insults would result in a decrease of plasma antioxidants. Previous acute exposure to CCl4 and ozone found that plasma concentrations of MDA and isoprostanes (measured by GC/MS) and urinary concentrations of isoprostanes (measured with an immunoassay) were increased in CCl4 treated rats in a time- and dose-dependent manner. All other products were not changed by CCl4 or showed only high-dose and/or single time point effects. In the ozone exposure model, however, plasma concentrations of MDA and isoprostanes (measured by GC/MS) were not changed whereas urinary concentrations of isoprostanes (measured with an immunoassay) were increased. Measures of oxidation products of proteins (protein carbonyls, methionine sulfoxidation, tyrosine oxidation products) and DNA (strand breaks, 8-OHdG, M1G) were not changed in a time-and dose-dependent manner by CCl4 and ozone. It is concluded that measurements of free radical mediated lipid peroxidation products - MDA and isoprostanes concentrations in plasma (by GC/MS) and urinary isoprostanes (by immunoassay or GC/MS) are promising candidates for general biomarkers of oxidative stress. The pattern of oxidative stress biomarkers seen in these three exposures will offer insight into the specificity and sensitivity of the markers and will provide evidence that a given product of oxidation may be a marker for some type of oxidative stress but not others.

我们现在在另外两种氧化应激实验动物模型中测量氧化应激有了新的发现：90天的异丙苯氢过氧化物皮肤暴露和LPS处理的小猪。采用新旧两种方法研究了这些氧化损伤对血浆和尿液中脂质氢过氧化物、TBARS、丙二醛（MDA）和异前列腺素浓度的时间和剂量依赖性影响。测定了蛋白质的氧化产物（蛋白质羰基、蛋氨酸亚砜化和酪氨酸氧化产物）和DNA（链断裂、8-OHdG和M1G）。此外，研究了两种暴露对血浆α -生育酚、辅酶Q （CoQ）、抗坏血酸、谷胱甘肽（GSH和GSSG）、尿酸和总抗氧化能力水平的时间和剂量依赖性影响，以确定不同损伤的氧化作用是否会导致血浆抗氧化剂降低。