The role of antioxidants in the long-term glycation of low density lipoprotein and its Cu2+-catalyzed oxidation

In the present study we investigated the influence of antioxidants such as EDTA, alpha-tocopherol, troglitazone and acetylsalicylic acid on the long-t erm-glycation of LDL and its copper ion-catalyzed oxidation. We observed th at (a) all antioxidants inhibited AGE-formation, while Amadori product form ation was only diminished by extreme concentrations of acetylsalicylic acid , (b) glycated LDL was more susceptible to copper-catalyzed oxidation than unglycated LDL, and (c) the oxidation of native LDL was more dramatically i nhibited by the antioxidants than that of glycated LDL. The observed differ ences may be a consequence of the significantly higher endogenous content i n hydroperoxides of glycated LDL as compared to native LDL. Therapeutic imp lications of these findings regarding vitamin E, which is supposed to slow atherogenesis and the development of microvascular complications in diabete s, are obvious: Vitamin E monotherapy, while blocking oxidative and AGE-mod ification of LDL, is unable to inhibit its AP-formation. As a consequence, tocopherol is susceptible to increased consumption by AP-associated radical production in hyperglycemic patients, which could be checked in part by th e tocopherol-protecting agent troglitazone and/or by acetylsalicylic acid.