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二氢硫辛酸对微粒体脂质过氧化的抗氧化活性及其对α-生育酚的依赖性。

Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol.

作者信息

Scholich H, Murphy M E, Sies H

机构信息

Institut für Physiologische Chemie I, Universität Düsseldorf, F.R.G.

出版信息

Biochim Biophys Acta. 1989 Feb 20;1001(3):256-61. doi: 10.1016/0005-2760(89)90108-2.

DOI:10.1016/0005-2760(89)90108-2
PMID:2492825
Abstract

The antioxidant effect of dihydrolipoate and lipoate was examined in microsomal fractions obtained from normal and alpha-tocopherol-deficient animals after initiation of lipid peroxidation with an NADPH/iron/ADP system. Dihydrolipoate prolonged the lag phase before the onset of low-level chemiluminescence and before the rapid accumulation of thiobarbituric acid-reactive substances in normal but not in vitamin E-deficient microsomes. Lipoate did not show such an antioxidant effect. It is concluded that the dihydrolipoate-mediated protection against lipid peroxidation by prolonging the lag phase is dependent on alpha-tocopherol. Likewise, dihydrolipoate prolonged the lag phase before the onset of the rapid loss of vitamin E during lipid peroxidation. Dihydrolipoate, like other biological thiols such as GSH, also affects the peroxidative process after the lag period. The effects included a smaller slope of the chemiluminescence increase, a lower maximal level of chemiluminescence, a slower loss of alpha-tocopherol and a slower accumulation, but unchanged maximal levels, of thiobarbituric acid-reactive substances. The biological significance may be most prominent in the mitochondrial matrix space, where lipoamide-containing ketoacid dehydrogenases are located. A potential pharmacological use of this biological dithiol in conditions associated with oxidative stress could be based on the antioxidant activity of dihydrolipoate.

摘要

在用NADPH/铁/ADP系统引发脂质过氧化后,研究了二氢硫辛酸和硫辛酸在从正常动物和α-生育酚缺乏动物获得的微粒体组分中的抗氧化作用。二氢硫辛酸延长了低水平化学发光开始前以及正常微粒体中硫代巴比妥酸反应性物质快速积累前的延迟期,但在维生素E缺乏的微粒体中没有这种作用。硫辛酸没有表现出这样的抗氧化作用。得出的结论是,二氢硫辛酸通过延长延迟期介导的对脂质过氧化的保护作用依赖于α-生育酚。同样,二氢硫辛酸延长了脂质过氧化过程中维生素E快速损失开始前的延迟期。二氢硫辛酸与其他生物硫醇如谷胱甘肽一样,在延迟期后也影响过氧化过程。这些影响包括化学发光增加的斜率较小、化学发光的最大水平较低、α-生育酚的损失较慢以及硫代巴比妥酸反应性物质的积累较慢,但最大水平不变。其生物学意义可能在线粒体基质空间最为突出,含硫辛酰胺的酮酸脱氢酶位于该空间。这种生物二硫醇在与氧化应激相关的病症中的潜在药理学用途可能基于二氢硫辛酸的抗氧化活性。

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