We appreciate the insightful comments by Dr. Kelley (1) regarding our study (2), which found that uricase-induced reduction in plasma uric acid (UA) concentrations decreased antioxidant capacity (AC) (assessed by measuring total radical-trapping antioxidant potential and ferric-reducing antioxidant potential in plasma and saliva) and markers of oxidative stress (urinary 8-iso-prostaglandin F2α and muscle carbonylated protein content), but did not affect insulin sensitivity (assessed by evaluating the increase in whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp procedure) (2). Dr. Kelley questions whether the decrease in AC and the increase in markers of oxidative stress were due to the generation of H2O2 that occurs during UA degradation, rather than the reduction in UA-mediated AC. We agree that the production of H2O2 induced by lowering UA by infusing uricase could have contributed to the effects we observed on AC and oxidative stress. However, this possibility does not diminish the importance of UA as a circulating antioxidant, which is estimated to provide ∼60% of the free-radical scavenging capacity in plasma (3). In addition, the human body produces considerable amounts of catalase and superoxide dismutases, which are potent scavengers of free radicals (4) and likely minimized the oxidant effect of H2O2 produced by the conversion of UA to allantoin. Nonetheless, it is important to appreciate that the major aim of our study was to determine the importance of oxidative stress in the pathogenesis of insulin resistance in obese people. Therefore, our finding that an acute uricase-induced increase in oxidative stress did not increase insulin resistance is still valid, independent of whether the increase in oxidative stress was induced by increased H2O2 production or decreased circulating UA.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.