Biomarkers Of Oxidative Stress Study

我们现在有新的发现，从测量氧化应激的两个额外的实验动物模型的氧化应激：90天的异丙苯过氧化氢皮肤暴露和LPS治疗的小型猪。这些氧化损伤的时间和剂量依赖性影响的血浆和尿液中的脂质过氧化氢，TBARS，丙二醛（MDA）和异前列腺素的浓度进行了研究与新旧技术。蛋白质（蛋白质羰基，甲硫氨酸磺基氧化和酪氨酸氧化产物）和DNA（链断裂，8-OHdG和M1 G）的氧化产物的措施进行了。此外，时间和剂量依赖性影响的两个曝光对血浆水平的α-生育酚，辅酶Q（辅酶Q），抗坏血酸，谷胱甘肽（GSH和GSSG），尿酸和总的抗氧化能力进行了研究，以确定是否不同的侮辱氧化作用会导致血浆抗氧化剂的减少。 先前急性暴露于CCl 4和臭氧发现，血浆中的MDA和异前列腺素的浓度（GC/MS测定）和尿中的异前列腺素的浓度（用免疫测定法测定）在CCl 4处理的大鼠中以时间和剂量依赖性的方式增加。所有其他产品均未被CCl 4改变或仅显示高剂量和/或单时间点效应。然而，在臭氧暴露模型中，MDA和异前列烷的血浆浓度（GC/MS测定）没有变化，而尿中异前列烷的浓度（用免疫测定法测定）增加。CCl 4和臭氧对蛋白质氧化产物（蛋白质羰基化、甲硫氨酸磺基氧化、酪氨酸氧化产物）和DNA氧化产物（链断裂、8-OHdG、M1 G）的影响不随时间和剂量的变化而变化。 它的结论是，自由基介导的脂质过氧化产物- MDA和异前列腺素的浓度在血浆（GC/MS）和尿中的异前列腺素（通过免疫测定或GC/MS）的测量是有前途的候选人的氧化应激的一般生物标志物。 在这三种暴露中观察到的氧化应激生物标志物的模式将提供对标志物的特异性和敏感性的深入了解，并将提供证据证明给定的氧化产物可能是某些类型的氧化应激的标志物，而不是其他类型的氧化应激的标志物。

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.