Kadiiska M B, Gladen B C, Baird D D, Germolec D, Graham L B, Parker C E, Nyska A, Wachsman J T, Ames B N, Basu S, Brot N, Fitzgerald G A, Floyd R A, George M, Heinecke J W, Hatch G E, Hensley K, Lawson J A, Marnett L J, Morrow J D, Murray D M, Plastaras J, Roberts L J, Rokach J, Shigenaga M K, Sohal R S, Sun J, Tice R R, Van Thiel D H, Wellner D, Walter P B, Tomer K B, Mason R P, Barrett J C
Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD F0-02, Research Triangle Park, NC 27709, USA.
Free Radic Biol Med. 2005 Mar 15;38(6):698-710. doi: 10.1016/j.freeradbiomed.2004.09.017.
Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.
作为寻找氧化应激非侵入性生物标志物的全面多实验室验证研究的一部分，对大鼠血液、血浆和尿液中脂质、蛋白质和DNA的氧化产物进行了测量。本文是全国氧化应激生物标志物研究的第二篇报告，该研究使用急性四氯化碳中毒作为氧化应激的啮齿动物模型。研究了四氯化碳对脂质氢过氧化物、硫代巴比妥酸反应物（TBARS）、丙二醛（MDA）、异前列腺素、蛋白质羰基、甲硫氨酸亚砜氧化、酪氨酸产物、8-羟基-2'-脱氧鸟苷（8-OHdG）、白细胞DNA-MDA加合物和DNA链断裂浓度的时间依赖性（2、7和16小时）和剂量依赖性（腹腔注射120和1200mg/kg）效应，以确定四氯化碳的氧化作用是否会导致这些氧化产物的生成增加。在多个时间点，低剂量和高剂量四氯化碳处理的大鼠血浆中MDA和异前列腺素（均通过气相色谱-质谱法测量）以及尿液中异前列腺素（通过免疫测定或液相色谱/串联质谱法测量）的浓度均升高。在测试的四种条件中的三种条件下，其他尿液标志物（MDA和8-OHdG）在处理后显示出显著升高。得出的结论是，血浆和尿液中MDA和异前列腺素以及尿液中8-OHdG的测量是氧化应激一般生物标志物的潜在候选物。所有其他产物未因四氯化碳而改变或显示出较少的显著影响。
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