Fujita Tadashi
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Yakugaku Zasshi. 2002 Mar;122(3):203-18. doi: 10.1248/yakushi.122.203.
It is well known that biomembranes and subcellular organelles are susceptible to lipid peroxidation. There is a steadily increasing body of evidence indicating that lipid peroxidation is involved in basic deteriorative mechanisms, e.g., membrane damage, enzyme damage, and nucleic acid mutagenicity. The formation of lipid peroxides can be induced by enzymatic or nonenzymatic peroxidation in the presence of oxygen. The mechanisms of formation and removal of reactive oxygen species, lipid peroxides, and free radicals in biological systems are briefly reviewed. In recent years, there has been renewed interest in the role played by lipid peroxidation in many disease states. Xanthine oxidase has been shown to generate reactive oxygen species, superoxide (O2-.), and hydrogen peroxide (H2O2) that are involved in the peroxidative damage to cells that occurs in ischemia-reperfusion injury. During ischemia, this enzyme is induced from xanthine dehydrogenase. We have shown that peroxynitrite (a reactive nitrogen species) has the potential to convert xanthine dehydrogenase to oxidase. The following biological effects of lipid peroxidation were found: a) the lipid peroxidation induced by ascorbic acid and Fe2+ affects the membrane transport in the kidney cortex and the cyclooxygenase activity in the kidney medulla, and b) the hydroperoxy adducts of linoleic acid and eicosapentaenoic acid inhibit the cyclooxygenase activity in platelets. The balance between the formation and removal of lipid peroxides determines the peroxide level in cells. This balance can be disturbed if cellular defenses are decreased or if there is a significant increase in peroxidative reactions. Once lipid peroxidation is initiated, the reactive intermediate formed induces cell damage.
众所周知，生物膜和亚细胞器易受脂质过氧化作用的影响。越来越多的证据表明，脂质过氧化作用参与了诸如膜损伤、酶损伤和核酸诱变等基本的退化机制。在有氧存在的情况下，脂质过氧化物的形成可由酶促或非酶促过氧化作用诱导。本文简要综述了生物系统中活性氧、脂质过氧化物和自由基的形成及清除机制。近年来，脂质过氧化作用在许多疾病状态中所起的作用再次引起了人们的关注。黄嘌呤氧化酶已被证明可产生活性氧、超氧阴离子（O2-.）和过氧化氢（H2O2），这些物质参与了缺血再灌注损伤中发生的细胞过氧化损伤。在缺血期间，这种酶由黄嘌呤脱氢酶诱导产生。我们已经表明，过氧亚硝酸盐（一种活性氮物质）有可能将黄嘌呤脱氢酶转化为氧化酶。发现脂质过氧化作用具有以下生物学效应：a）抗坏血酸和Fe2+诱导的脂质过氧化作用影响肾皮质的膜转运和肾髓质的环氧化酶活性，b）亚油酸和二十碳五烯酸的氢过氧化物加合物抑制血小板中的环氧化酶活性。脂质过氧化物的形成与清除之间的平衡决定了细胞中的过氧化物水平。如果细胞防御能力下降或过氧化反应显著增加，这种平衡就会被打破。一旦脂质过氧化作用开始，形成的反应中间体就会诱导细胞损伤。
