The effects of free radical scavengers on the oxidation of low-density lipoproteins by macrophages.

Oxidised LDL has been implicated in the pathogenesis of atherosclerosis. Macrophages can oxidatively modify low-density lipoprotein (LDL) in vitro. The mechanisms of this oxidation process are presently unclear. In this study, we have investigated the effects of compounds and enzymes widely used to quench or scavenge active oxygen species to try to identify the oxidative species involved in this process. The data obtained suggest that hydrogen peroxide may possibly play a role in LDL oxidation by macrophages, whereas singlet oxygen and hydroxyl radicals may not. The role of superoxide anions was uncertain because copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese SOD (Mn-SOD), widely used to determine superoxide-dependency in other systems may be unsuitable in this particular system. Cu/Zn-SOD at high concentrations displayed a variability in its effects, sometimes augmenting LDL oxidation and sometimes inhibiting it. In the experiments in which Cu/Zn-SOD augmented LDL oxidation, heat inactivation of the enzyme decreased the augmentation; in the experiments in which Cu/Zn-SOD inhibited LDL oxidation, it retained its inhibitory effect after heat inactivation. Mn-SOD always inhibited modification even after heat inactivation. We have therefore concluded that superoxide involvement in LDL oxidation by macrophages is still uncertain and the uncertainty will remain until a suitable probe is found.