Glantzounis G K, Tsimoyiannis E C, Kappas A M, Galaris D A
University Department of Surgery, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
Curr Pharm Des. 2005;11(32):4145-51. doi: 10.2174/138161205774913255.
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. ischaemia-reperfusion 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.
尿酸是人体嘌呤代谢的终产物。其生成的最后两步反应，即催化次黄嘌呤转化为黄嘌呤以及后者转化为尿酸的反应，由黄嘌呤氧化还原酶催化，该酶可呈现两种可相互转化的形式，即黄嘌呤脱氢酶或黄嘌呤氧化酶。后者利用分子氧作为电子受体，生成超氧阴离子和其他活性氧产物。尿酸在与氧化应激相关的病症中的作用尚不完全清楚。主要基于流行病学研究的证据表明，血清尿酸水平升高是心血管疾病的一个危险因素，而氧化应激在其病理生理过程中起重要作用。此外，别嘌醇作为一种黄嘌呤氧化还原酶抑制剂，可降低血清尿酸水平，在与氧化应激相关的情况（如缺血-再灌注损伤、心血管疾病）中发挥保护作用。然而，越来越多的实验和临床证据表明，尿酸在体内作为一种抗氧化剂具有重要作用。本综述介绍了目前关于尿酸抗氧化作用的证据，并表明其作为氧化应激标志物具有重要作用，作为抗氧化剂具有潜在的治疗作用。需要进一步设计良好的临床研究来阐明尿酸（或尿酸前体）在与氧化应激相关疾病中的潜在用途。
