PHYSIOLOGICAL LEVELS OF ASCORBATE INHIBIT THE OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN

Oxidatively modified low density lipoprotein (LDL) could contribute to the atherosclerotic process by its cytotoxic effect, uptake by the scavenger receptor and influence on monocyte and macrophage motility. The aim of the present study was to examine the effect of physiologic levels of α-tocopherol and ascorbate on Cu2+-induced oxidative modification of LDL. Whereas α-tocopherol had an inhibitory effect on the oxidative modification of LDL only for 5 h, as evidenced by the electrophoretic mobility and lipid peroxide content, ascorbate inhibited the oxidative modification of LDL for both 5 and 24 h. By inhibiting the oxidative modification of LDL, ascorbate prevented the uptake and degradation of oxidatively modified LDL by the scavenger-receptor mechanism of cultured human monocyte derived macrophages. It thus appears that in this cell-free system (2.5 μM Cu2+), ascorbate is a more potent antioxidant than α-tocopherol. These findings indicate that ascorbate in physiologic concentrations should inhibit the oxidate modification of LDL in vivo. © 1990.