Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress

Jacob George, Allan D Struthers, Jacob George, Allan D Struthers

Abstract

Oxidative stress plays an important role in the progression of vascular endothelial dysfunction. The two major systems generating vascular oxidative stress are the NADPH oxidase and the xanthine oxidase pathways. Allopurinol, a xanthine oxidase inhibitor, has been in clinical use for over 40 years in the treatment of chronic gout. Allopurinol has also been shown to improve endothelial dysfunction, reduce oxidative stress burden and improve myocardial efficiency by reducing oxygen consumption in smaller mechanistic studies involving various cohorts at risk of cardiovascular events. This article aims to explain the role of xanthine oxidase in vascular oxidative stress and to explore the mechanisms by which allopurinol is thought to improve vascular and myocardial indices.

Keywords: allopurinol; vascular endothelial dysfunction; vascular oxidative stress.

Figures

Figure 1
Figure 1
The purine degradation pathway. Reproduced with permission from Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004; 555(Pt 3):589–606. Copyright © Blackwell Publishing.
Figure 2
Figure 2
Mechanism of xanthine oxidoreductase XOR reaction with xanthine; A) reductive half reaction; B) oxidative half reaction. Reproduced with permission from Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004; 555(Pt 3):589–606. Copyright © Blackwell Publishing.

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