EFFECTS OF ANTIOXIDANTS ON THE OXIDATIVE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN

An important event in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low-density lipoprotein (LDL) init iated by a free radical-driven lipid peroxidation process. Vitamin E a cts as a lipophilic chain-breaking antioxidant, while water-soluble ch ain-breaking antioxidants such as vitamin C or uric acid suppress the oxidation of LDL initiated by aqueous radicals. In this study, we esta blished a new method of measuring the lag time of inhibited lipid pero xidation using the lipophilic azo radical initiator V-70: 2-2'-azobis( 4-methoxy-2,4-dimethylvaleronitrile) and investigated in vitro the sus ceptibility of LDL to oxidation using this method when lipid-and water -soluble antioxidants were added. When the lipid-soluble antioxidant, vitamin E, was added to LDL, the lag time was extended whereas a highe r dose of vitamin E led to a shortened lag time of V-70-induced lipid peroxidation in LDL, These results suggest that vitamin E radicals (to copheroxyl radicals) act as prooxidants during the autoxidation of LDL . It was also shown that the shortened lag time induced by higher dose s of vitamin E was restored when lipid-and water-soluble antioxidants were added simultaneously, which suggests that vitamin E radicals deri ved from vitamin E are subsequently reduced by vitamin C to regenerate vitamin E. Thus, the interaction between lipid-and water-soluble anti oxidants provides an important function in maintaining LDL resistance to oxidation.