Biomarkers of Oxidative Stress Study

作为一项全面的、多实验室验证研究的一部分，对大鼠血浆中的抗氧化剂进行了测量，以寻找氧化应激的非侵入性生物标志物。在这项初步研究中，我们研究了一种CCl4中毒的动物模型。给药时间(2、7、16h)和剂量(120 mg/kg、1200 mg/kg，i.p.)研究了CCl4对血浆α-生育酚、抗坏血酸、谷胱甘肽(GSH和GSSG)、尿酸和总抗氧化能力的依赖性影响，以确定CCl4的氧化作用是否会导致血浆中抗氧化剂的损失。CCl4处理的大鼠的α-生育酚浓度降低。然而，由于伴随而来的胆固醇和甘油三酯的降低，不可能将α-生育酚的氧化与普遍的血脂变化分开。抗坏血酸水平在治疗的最早时间点较高；GSH/GSSG比值普遍下降，尿酸保持不变。总抗氧化能力除高剂量后16h升高外，其余时间无明显变化。这些结果表明，由于肝脏功能障碍和肝细胞破裂引起的血浆变化阻碍了对血浆抗氧化状态任何潜在变化的检测。

Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for non-invasive biomarkers of oxidative stress. For this initial study an animal model of CCl4 poisoning was studied. The time-(2, 7 and 16 h) and dose-(120 mg/kg and 1200 mg/kg, i. p.) dependent effects of CCl4 on plasma levels of alpha-tocopherol, ascorbic acid, glutathione (GSH and GSSG), uric acid and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl4 would result in losses of antioxidants from plasma. The alpha-tocopherol concentration was decreased in CCl4-treated rats. However, due to concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of alpha-tocopherol from generalized lipid changes. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes due to liver malfunction and rupture of liver cells impede detection of any potential changes in the antioxidant status of the plasma.