Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress.

Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress.
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DOI:
10.1016/j.freeradbiomed.2015.01.006
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发表时间:
2015-04
影响因子:
7.4
通讯作者:
Mason, Ronald P.
Mason, Ronald P.
中科院分区:
医学1区
文献类型:
--
作者:
Kadiiska, Maria B.;Peddada, Shyamal;Herbert, Ronald A.;Basu, Samar;Hensley, Kenneth;Jones, Dean P.;Hatch, Gary E.;Mason, Ronald P.

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这是一系列出版物中的最新报告,旨在确定一种基于血液的抗氧化生物标志物,可以作为体内氧化应激的指标。该研究的目的是测试将哥廷根小型猪剧烈暴露于内毒素脂多糖(LPS)中是否会导致血浆中抗氧化剂的损失。我们设定了一项标准,即应在血浆中测量显着效果,并在两种剂量和多个时间点观察到显着效果。给动物静脉内注射 2.5 和 5 μg/kg 两剂 LPS。在注射 LPS 之前从每只动物收集对照血浆。 LPS注射后,在2小时、16小时、48小时和72小时收集血浆样品。与同一时间点的对照组相比,任一剂量在多个时间点均未发现以下任何潜在标志物出现统计学上的显着损失:抗坏血酸、生育酚(α、δ、γ)、GSH/GSSG 比率、半胱氨酸/胱氨酸(Cys/CySS)、混合二硫化物和总抗氧化能力。但尿酸、总GSH、总Cys明显升高,可能是LPS对肝脏有损害作用所致。受损细胞中的物质泄漏到血浆中可能会增加血浆抗氧化剂的浓度,从而使变化难以检测。虽然本研究使用了LPS诱导的氧化应激的小型猪动物模型,但它证实了我们之前在不同大鼠模型中的发现,即血浆中抗氧化剂的测量对于评估体内氧化损伤没有用处。
This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point. Animals were injected with two doses of LPS at 2.5- and 5 μg/kg i.v. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2 h, 16 h, 48 h and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (α, δ, γ), ratios of GSH/GSSG, cysteine/cystine (Cys/CySS), mixed disulfides and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had harmful effect on liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidants concentrations making changes difficult to detect. Although this study used a mini pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models, that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.
DOI: 10.1073/pnas.78.11.6858
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