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

维生素E抑制脂质过氧化次级反应的研究

• 批准号: 18580115
• 负责人: YAMAUCHI Ryo
• 金额: $ 2.48万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18580115/
• 关键词: vitamin E; lipid peroxidation; γ-tocopherol; 4-oxo-2-nonenal; 4-hvoiroxv-2-nonenal; 4-オキソ-2-ノネナール

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.

过氧化过程中不饱和脂质的氧化裂解产生细胞毒性和基因毒性的α,β-不饱和醛，例如4-羟基-2-壬烯醛（HNE）和4-氧代-2-壬烯醛（ONE）我们研究了其反应性。维生素E与HNE或ONE一起阐明维生素E对α,β-不饱和醛的解毒作用。最活跃的维生素E（α-TH）不与这些醛发生反应，而γ-和δ-TH在酸性条件下可以与ONE或HNE反应，ONE是已知的仲醛中反应性最强的醛。因此，我们研究了 y-TH 与 ONE 的反应产物，当 y-TH 与 ONE 在 HCl 存在下于 37℃ 反应时，产物出现峰值。通过反相HPLC检测化合物1-3并通过NMR确定其结构，确定化合物1为5-(1-(呋喃-2-基)戊基)-γ-生育酚， y-TH 与 ONE 的加成产物也是 y-TH 与 ONE 的加成产物，其中 y-TH 的 C-5 位和 6-羟基基团与 y-TH 结合。 ONE 的 C-5 和 C-4 位是 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 位与另一个 ONE 分子的 C-5 位结合。 S-TH也可以与ONE反应形成一些加成产物，但其结构仍未知。结果表明，苯并二氢吡喃环中具有亲核特性的y-和8-TH可以充当亲脂性的清除剂。 ONE.y-TH 等亲电子试剂是植物种子中维生素 E 的主要形式，因此在我们的饮食中，γ-TH 可能会捕获膜溶性 α,β-不饱和醛，在其形成之前形成不反应的碳中心加合物。会损害重要的生物分子。