Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification

Several lines of evidence indicate that the oxidative modification of low density lipoproteins (LDL) may provide an important link between plasma LDL and the genesis of the atherosclerotic lesion. Ascorbate is an important water-soluble, chain-breaking antioxidant in humans. Probucol, a lipid-soluble antioxidant drug has been shown to retard the progression of atherosclerosis. The aim of the present study was to compare the effects of probucol and physiologic levels of ascorbate on the oxidative modification of LDL in both a cell-free (2.5 μM Cu⁺⁺ in phosphate-buffered saline) and cellular system (human monocyte macrophages in Ham's F-10 medium). Both ascorbate and probucol inhibited the oxidative modification of LDL in both systems to a similar degree as evidenced by the thiobarbituric acid-reacting substance activity, electrophoretic mobility, and degradation by macrophages. However, whereas co-incubation with physiologic levels of ascorbate resulted in a substantial preservation of the α-tocopherol, γ-tocopherol, and β-carotene of the LDL, probucol in concentrations ranging from 10 to 80 μM failed to protect these antioxidants. Thus, in addition to being as potent as probucol in inhibiting the oxidation of LDL, ascorbate in contrast preserves the endogenous antioxidants in the LDL.