Inhibitory effects of fluvastatin and its metabolites on hydrogen peroxide-induced oxidative destruction of hemin and low-density lipoprotein.
Inhibitory effects of fluvastatin and its metabolites on hydrogen peroxide-induced oxidative destruction of hemin and low-density lipoprotein.
复制标题
氟伐他汀及其代谢物对过氧化氢诱导的血红素和低密度脂蛋白氧化破坏的抑制作用。
DOI：
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发表时间：
2000
影响因子：
2
通讯作者：
Hiroshi Narita
中科院分区：
文献类型：
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作者：
K. Suzumura;Keiko Tanaka;Mikiko Yasuhara;Hiroshi Narita
一些用作降血脂药物的3-羟基-3-甲基戊二酰辅酶A （HMG-CoA）还原酶抑制剂在体内给药时，有可能降低血浆低密度脂蛋白（LDL）的氧化性。其体内机制被认为与其基于HMG-CoA还原酶抑制活性的降血脂作用密切相关。我们推测，某些类型的HMG-CoA还原酶抑制剂在体内具有抑制LDL氧化的额外机制，这不是由于其降血脂作用，而是由于其基于其独特化学结构的直接抗氧化作用。我们在体外直接比较了著名的HMG-CoA还原酶抑制剂（氟伐他汀、普伐他汀、辛伐他汀、西伐他汀和阿托伐他汀）对过氧化氢诱导的血红蛋白和LDL氧化破坏的抗氧化作用。氟伐他汀对该系统无抑制作用。它的效果是剂量依赖性的，几乎和天然抗氧化剂、α -生育酚和抗坏血酸一样强。此外，M2是氟伐他汀的羟基化代谢物，显示出比氟伐他汀更强的抗氧化活性。我们认为，在这些HMG-CoA还原酶抑制剂中，氟伐他汀不仅具有降血脂作用，而且具有直接的抗氧化作用，尤其具有抑制LDL氧化的能力。
Some 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are used as hypolipidemic drugs, have been reported to have the potential to reduce the oxidizability of plasma low-density lipoprotein (LDL) when they are administered in vivo. Their in vivo mechanism is believed to be closely related to their hypolipidemic action based on the HMG-CoA reductase inhibitory activity. We hypothesized that some type of HMG-CoA reductase inhibitor has additional mechanism inhibiting LDL oxidation in vivo due not to its hypolipidemic action but to its direct antioxidative effect based on its unique chemical structure. We directly compared in vitro the antioxidative effects of well-known HMG-CoA reductase inhibitors (fluvastatin, pravastatin, simvastatin, cerivastatin and atorvastatin) on the hydrogen peroxide-induced oxidative destruction of hemin and LDL. Fluvastatin but not the others showed the inhibitory effect on this system. Its effect was dose-dependent and almost as strong as the natural antioxidants, alpha-tocopherol and ascorbic acid. Further, M2, which is a hydroxylated metabolite of fluvastatin, showed stronger antioxidative activity than did fluvastatin. We suggest that among these HMG-CoA reductase inhibitors, fluvastatin especially has an ability to retard the LDL oxidation which is based on not only its hypolipidemic action but also its direct antioxidative effect.