Uric Acid and Oxidative Stress
G. K. Glantzounis, E. C. Tsimoyiannis, A. M. Kappas and D. A. Galaris
Affiliation: University Department of Surgery, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemiareperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.
Keywords: Uric acid, oxidative stress, xanthine oxidoreductase, xanthine oxidase, xanthine dehydrogenase, allopurinol, ischaemia-reperfusion, peroxynitrite
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