Modeling the interaction of peroxynitrite with low-density lipoproteins. III: The role of antioxidants

Peroxynitrite is a candidate for the substance responsible for the initiation of peroxidation of low-density lipoproteins (LDL) in blood. This is believed to be the initial step in the formation of atherosclerotic plaque. Using kinetic arguments, this paper examines possible routes in both LDL particles and in the surrounding plasma for antioxidants to block peroxidation. The antioxidants considered include ascorbate ion, glutathione and human serum albumin in plasma as well as a-tocopherol, ubiquinone-10 and carotenoids in the LDL particles. The results suggest that in the plasma compartment the most efficacious blocking mechanism is the reaction of ascorbate ion with the peroxynitrite precursor, superoxide ion. The situation in LDL particles is much less clear cut because of the paucity of kinetic data in this medium. However, some constraints are suggested on the requirements for an effective antioxidant. (C) 2000 Academic Press.