ANTIOXIDANT ACTIVITY OF ALLOPURINOL ON COPPER-CATALYZED HUMAN LIPOPROTEIN OXIDATION

We found that allopurinol, at therapeutically relevant concentrations (9-58 mu M), significantly counteracted copper-catalysed human non-HDL lipoprotein oxidation, as assessed by thiobarbituric acid reactant co ntent and kinetics of conjugated diene formation. Oxypurinol was ineff ectual. Both drugs had no activity on metal-independent, peroxyl radic al-induced lipoprotein oxidation. Specific fluorescence-quenching expe riments revealed that only allopurinol could interact with copper anta gonizing metal binding to lipoproteins. Thus, therapeutic allopurinol concentrations can inhibit copper-catalysed lipoprotein oxidation thro ugh metal complexation, suggesting some antioxidant-antiatherogenic ac tivity of the drug in vivo. (C) 1997 Federation of European Biochemica l Societies.