Oxidation of low-density lipoprotein (LDL) has been recognized as playing an important role in the development and progression of atherosclerotic heart disease. Human LDL was isolated and challenged with a range of oxidants either in the presence or absence of AGE or its diethyl ether extract. Oxidative modification of the LDL fraction using CuSO(4), 5-lipoxygenase and xanthine/xanthine oxidase was monitored by both the appearance of thiobarbituric-acid substances (TBA-RS) and an increase in electrophoretic mobility.This study indicates that AGE is an effective antioxidant as it scavenged superoxide ions and reduced lipid peroxide formation in cell free assays. Superoxide production was completely inhibited in the presence of a 10% (v/v) aqueous preparation of AGE and reduced by 34% in the presence of a 10% (v/v) diethyl ether extract of AGE. The presence of 10% (v/v) diethyl ether extract of AGE significantly reduced Cu(2+) and 15-lipoxygenase-mediated lipid peroxidation of isolated LDL by 81% and 37%, respectively. In addition, it was found that AGE also had the capacity to chelate copper ions. In contrast, the diethyl ether extract of AGE displayed no copper binding capacity, but demonstrated distinct antioxidant properties. These results support the view that AGE inhibits the in vitro oxidation of isolated LDL by scavenging superoxide and inhibiting the formation of lipid peroxides. AGE was also shown to reduce LDL oxidation by the chelation of Cu(2+). Thus, AGE may have a role to play in preventing the development and progression of atherosclerotic disease.