Physiologic Levels of Uric Acid Inhibit Xanthine Oxidase in Human Plasma

Abstract

Xanthine oxidase, a key source of reactive oxygen species, and purine substrates are detected in the circulation after ischemia-reperfusion. High levels of uric acid, produced by a xanthine oxidase-catalyzed reaction, are found in human plasma. We studied whether uric acid could alter xanthine oxidase activity in plasma obtained from eight adults and eight neonates. Known amounts of uric acid were added to xanthine and xanthine oxidase-supplemented buffer and plasma, and the production of uric acid and superoxide was determined. Uric acid, 150 and 300 microM, decreased the oxidation of xanthine to uric acid in adult plasma by 37.5 +/- 5.6 and 48.9 +/- 6.1% and formation of superoxide by 23.2 +/- 1.9 and 32.0 +/- 2.3%, respectively, compared with plasma without uric acid. In newborn plasma, a similar pattern and extent of inhibition was observed. Superoxide formation, however, was inhibited to a greater extent than in adult plasma. Endogenous xanthine oxidase was detected in newborn plasma in nine additional neonates using HPLC. These results indicate that uric acid is an effective inhibitor of the formation of superoxide and hydrogen peroxide by xanthine oxidase at the levels found in human plasma. Plasma uric acid may play an important role in attenuating the oxidant-mediated tissue damage caused by xanthine oxidase released into the circulation during ischemia-reperfusion.