Inhibitory effects of α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl)benzeneacetic acid on Cu~(2+) and Fe~(2+) induced oxidative modification of human low density lipoprotein

为观察α－甲基－４－（３－氧－２Ｈ－１，２－苯并异硒唑－２－基）苯乙酸（ＭＢＢＡ）对Ｃｕ２＋及Ｆｅ２＋氧化修饰低密度脂蛋白（ＬＤＬ）的保护作用及其作用机理，采用分光光度法测定ＬＤＬ中丙二醛（ＭＤＡ）和共轭双烯（ＣＤ）的产生量．ＭＢＢＡ（０．２－２μｍｏｌ·Ｌ－１）能以剂量依赖性抑制Ｃｕ２＋及Ｆｅ２＋诱导的ＭＤＡ和ＣＤ生成．２μｍｏｌ·Ｌ－１的ＭＢＢＡ对Ｃｕ２＋诱导ＬＤＬ产生ＭＤＡ和ＣＤ的抑制率分别为８９．７％和６０．３％．０．５ｍｍｏｌ·Ｌ－１ＧＳＨ对ＬＤＬ产生ＭＤＡ无影响，但能显著增强ＭＢＢＡ对ＭＤＡ生成的抑制作用．上述结果表明ＭＢＢＡ对ＬＤＬ氧化修饰的抑制作用可能依赖于其ＧＳＨ－Ｐｘ样活性的作用和（或）直接还原脂质氢过氧化物的作用．

Inhibitory effects of α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl)-benzeneacetic acid on Cu~2+ and Fe~2+ induced oxidative modification of human low density lipoprotein

To examine the protective effect of α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl)-benzeneacetic acid (MBBA) on Cu2+ and Fe2+ induced oxidation of low density lipoprotein(LDL) and its possible mechanism, the contents of malondialdehyde(MDA) and conjugated dienes(CD) in LDL suspensions were measured by spectrophotometric methods to assess the oxidation of LDL. Both MDA and CD formations in Cu~2+ or Fe~2+ treated LDL were increased markedly. MBBA(0.2-2 μmol·L 1) inhibited MDA and CD formations in LDL induced by Cu~2+ or Fe~2+ in a concentration dependent manner. The inhibitory rates of 2 μmol·L 1 MBBA on 5 μmol·L 1 Cu~2+ induced MDA and CD formation were 89.7% and 60.3% respectively. Reduced glutathione(GSH) 0.5 mmol·L 1 alone had no effect on MDA and CD formation, but it significantly enhanced the inhibitory effect of MBBA. The results suggest that the antioxidant effect of MBBA on human LDL oxidation probably depends both on its GSH peroxidase mimetic activity (dependent of GSH) and on its direct reductive action against LDL oxidation (independent of GSH).