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 Cu2+-catalyzed LDL oxidation. Oxidative modification of LDL was monitored by assaying intermediates and end products of lipid peroxidation, conjugated dienes (GD), 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 μM) 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 α-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. Separation of AMG from LDL by gel chromatography largely restored the lipid peroxides and REM of oxidized LDL. Thus AMG interferes with these assays of lipid peroxidation. In comparison with ascorbate, which inhibits LDL oxidation at physiologic levels, the significance of a partial inhibition of some indices of LDL oxidation by high levels of aminoguanidine (20 mM) remains to be established.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Lipid Research|
|State||Published - 1994|
- LDL oxidation
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