Ascorbate prevents prooxidant effects of urate in oxidation of human low density lipoprotein

Abstract

Uric acid and ascorbic acid are important low molecular weight antioxidants in plasma. Their interactions and combined effect on Cu(2+)-catalysed oxidation of human low density lipoprotein were studied in vitro. It was found that uric acid alone becomes strongly prooxidant whenever it is added to low density lipoprotein shortly after the start of oxidation (conditional prooxidant). Ascorbic acid, which is present in human plasma at much lower concentrations (20-60 microM) than urate (300-400 microM), is in itself not a conditional prooxidant. Moreover, ascorbate prevents prooxidant effects of urate, when added to oxidising low density lipoprotein simultaneously with urate, even at a 60-fold molar excess of urate over ascorbate. Ascorbate appears to have the same anti-prooxidant effect with other aqueous reductants, which, besides their antioxidant properties, were reported to be conditionally prooxidant. Such interactions between ascorbate and urate may be important in preventing oxidative modification of lipoproteins in the circulation and in other biological fluids.