Involvement of Oxygen Radicals in Aging

由于物种的寿命与其代谢率呈负相关，因此认为氧自由基应参与衰老过程。组织氧化损伤的直接证据之一是正常人血浆中存在胆固醇酯氢过氧化氢。这种氢过氧化氢在大鼠血浆中的水平高于人类。这一结果表明氧化应激与衰老呈正相关。同样有趣的是，高蛋白血症大鼠对某些胺的致癌非常敏感，其过氧化氢水平较高。下一步，我可以开发出检测磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰肌醇和心磷脂等磷脂过氧化氢的方法。而在大鼠肝脏和心脏中未检测到磷脂过氧化产物。这可能是由于谷胱甘肽过氧化物酶还原过氧化氢所致，因此，有必要对游离脂肪酸的氧化产物进行检测。研究发现，单丹西维林对它们的衍生化非常有用，在氧化应激大鼠体内，其中一种氧化产物增加了皮摩尔的水平。

It is considered that oxygen radicals should be involved in the aging process since the life time of species inversely correlates with metabolic rates of them. One of the direct evidence for the oxidative damage of the tissue is the presence of cholesteryl ester hydroperoxide in normal human plasma. This hydroperoxide levels in rat plasmas are higher than those in humans. This results indicate the positive correlation between the oxidative stress and aging. It is also interesting that analbuminemic rats, which is very susceptible to the induction of cancers by certain amines, have higher hydroperoxide levels.Next I could develop the method for the detection of hydroperoxides of phospholipids such as phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. However, no phospholipid hydroperoxides were detected in rat liver and heart. This is likely due to the reduction of the hydroperoxides by glutathione peroxidase.Therefore, it is necessary to detect the oxidation products of free fatty acids. It is found that the derivatization of them by monodansylcadaverine is very useful for the picomole level detection and one of the oxidation products increased in the rats under oxidative stress.