Studies on the inhibitory effect of vitamin E against secondary reaction of lipid peroxidation

不饱和脂质在过氧化过程中的氧化裂解产生细胞毒性和遗传毒性a，β-不饱和醛，如4-羟基-2-壬烯醛（HNE）和4-氧-2-壬烯醛（ONE）。我们研究了维生素E与HNE或ONE的反应性，以阐明维生素E对α，β-不饱和醛解毒的作用。在酸性条件下，活性最强的维生素E Α-Tocopherol （α-TH）不与这些醛发生反应，而y-和δ- th可与ONE或HNE发生反应。已知ONE是脂质过氧化产物中活性最强的醛。因此，对y-TH与ONE的反应产物进行了研究。在HC1存在下，y-TH与ONE在37℃下反应，用反相高效液相色谱法检测到产物峰1-3。分离得到化合物1 ~ 3，并通过NMR对其结构进行了表征。化合物1为5-（1-（呋喃-2-基）戊基）-y-生育酚，y-TH与ONE加成产物。化合物2也是y-TH与ONE的加成产物，其中y-TH的C-5位和6-羟基与ONE的C-5和C-4位结合。化合物3是γ-TH与两个ONE分子的加成产物，其中化合物2中ONE残基的C-1位置与另一个ONE分子的C-5位置结合。S-TH还能与ONE反应生成一些加成产物，但其结构尚不清楚。结果表明，在染色质环上具有亲核性质的y-和8-THs可以作为亲脂性亲电试剂（如ONE）的清除剂。y-TH是植物种子中维生素E的主要形式，因此也存在于我们的饮食中。因此，γ-TH可以在膜溶性α，β-不饱和醛破坏重要生物分子之前捕获它们，形成不反应的碳中心加合物。

Oxidative cleavage of unsaturated lipids during peroxidation gives rise to cytotoxic and genotoxic a,β-unsaturated aldehydes, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). We have studied the reactivity of vitamin E with HNE or ONE to clarify the role of vitamin E on the detoxification of α,β-unsaturated aldehydes. Α-Tocopherol (α-TH), the most active vitamin E, did not react with these aldehydes, whereas y- and δ- THs could react with ONE or HNE under the acidic conditions. ONE is known to be the most reactive aldehyde among the secondary of lipid peroxidation products. Therefore, the reaction products of y-TH with ONE have been investigated. When y-TH was reacted with ONE at 37℃ in the presence of HC1, product peaks 1-3 were detected by reversed-phase HPLC. Compounds 1-3 were isolated and their structures were determined by NMR. Compound 1 was determined to be 5- (1- (furan-2-yl) pentyl) -y-tocopherol, the addition product of y-TH with ONE. Compound 2 was also the addition product of y-TH with ONE where the C-5 position and 6-hydroxyl group of y-TH were bound to the C-5 and C-4 positions of ONE. Compound 3 was the addition product of γ-TH with two ONE molecules where the C-1 position of ONE residue in compound 2 was bound to the C-5 position of another ONE molecule. S-TH could also react with ONE to form some addition products although their structures were still unknown. The results indicate that y- and 8-THs which possess nucleophilic character in the chroman ring can act as scavengers of lipophilic electrophiles such as ONE.y-TH is the major form of vitamin E in plant seeds and consequently in our diet. Thus, γ-TH may trap the membrane-soluble α,β-unsaturated aldehydes to form unreactive carbon-centered adducts before they can damage important biological molecules.