Scaccini C, Chiesa G, Jialal I
Center for Human Nutrition, University of Texas, Southwestern Medical Center at Dallas 75235.
J Lipid Res. 1994 Jun;35(6):1085-92.
Several lines of evidence support a role for oxidized low density lipoprotein (LDL) in the genesis of the atherosclerotic lesion. Hence, the effect of compounds with antioxidant properties on LDL oxidation assumes great significance. Ascorbate, a potent water-soluble chain-breaking antioxidant, has been shown to inhibit LDL oxidation. Aminoguanidine (AMG) is a pharmacological inhibitor of advanced non-enzymatic glycosylation. Recently it has been suggested that aminoguanidine might have an inhibitory effect on LDL oxidation, but total lipid peroxidation assayed by conjugated diene formation was not inhibited. Thus, in this study, we compared the effect of aminoguanidine with ascorbate to obtain a better appreciation of the effect of AMG on Cu(2+)-catalyzed LDL oxidation. Oxidative modification of LDL was monitored by assaying intermediates and end products of lipid peroxidation, conjugated dienes (CD), lipid peroxides (LPO), and relative electrophoretic mobility (REM). Apolipoprotein B-100 modification (increased fluorescence, fragmentation on SDS-PAGE, and 125I-labeled LDL degradation by human macrophages) was also measured. Ascorbate (100 microM) inhibited LDL oxidation by > 95%, as evidenced by all of the selected indices. Aminoguanidine (20 mM) substantially decreased thiobarbituric acid-reactive substances (TBARS) activity and lipid peroxide formation, but only partially prevented the increase of REM (-55%), apoB fluorescence (-39%), and degradation by macrophages (-54%). Unlike ascorbate, AMG failed to preserve alpha-tocopherol in LDL, prevent apoB-100 fragmentation, or inhibit conjugated diene formation during LDL oxidation. Furthermore, incubation of AMG with already oxidized LDL resulted in a significant decrease in TBARS activity and LPO, and 26.9% decrease in the REM of LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
多条证据支持氧化型低密度脂蛋白（LDL）在动脉粥样硬化病变发生过程中起作用。因此，具有抗氧化特性的化合物对LDL氧化的影响具有重要意义。抗坏血酸是一种有效的水溶性链断裂抗氧化剂，已被证明可抑制LDL氧化。氨基胍（AMG）是晚期非酶糖基化的药理学抑制剂。最近有人提出氨基胍可能对LDL氧化有抑制作用，但通过共轭二烯形成测定的总脂质过氧化并未受到抑制。因此，在本研究中，我们比较了氨基胍和抗坏血酸的作用，以更好地了解AMG对铜（2+）催化的LDL氧化的影响。通过测定脂质过氧化的中间体和终产物、共轭二烯（CD）、脂质过氧化物（LPO）和相对电泳迁移率（REM）来监测LDL的氧化修饰。还测量了载脂蛋白B-100的修饰（荧光增加、SDS-PAGE上的片段化以及人巨噬细胞对125I标记的LDL的降解）。所有选定指标均表明，抗坏血酸（100 microM）可抑制LDL氧化>95%。氨基胍（20 mM）可显著降低硫代巴比妥酸反应性物质（TBARS）活性和脂质过氧化物的形成，但仅部分阻止REM的增加（-55%）、载脂蛋白B荧光（-39%）和巨噬细胞降解（-54%）。与抗坏血酸不同，AMG未能在LDL中保留α-生育酚，未能防止载脂蛋白B-100片段化，也未能在LDL氧化过程中抑制共轭二烯的形成。此外，将AMG与已氧化的LDL一起孵育会导致TBARS活性和LPO显著降低，LDL的REM降低26.9%。（摘要截短于25
