Effect of pharmacological lowering of plasma urate on exercise-induced oxidative stress

Abstract

Urate is a metabolic end product of purine metabolism that contributes about 66% of the antioxidant capacity of plasma. The objective of this study was to evaluate the importance of plasma urate as an antioxidant using pharmacological lowering and examining the impact on plasma antioxidant capacity and oxidative stress after intense exercise. Fifteen subjects ran for 45 min at ~80% VO2 max under the influence of probenecid (1 g/d) (PRO) or placebo (PLA) in a double-blind, crossover design. Blood samples obtained at baseline, pre-exercise, and immediately post-exercise were analyzed for F2-isoprostanes, lipid hydroperoxides (LHs), ferric-reducing ability of plasma (FRAP), urate, ascorbate (AA), and nitrite. A 2 (group) × 2 (time) repeated-measures analysis of variance (ANOVA), one-way ANOVA, Tukey–Kramer multiple comparison tests, and Student’s t tests were used for statistical analysis. PRO exhibited lowered urate and FRAP compared with baseline (p ≤ 0.05), and group effects existed for the exercise trials (p = 0.023 and p ≤ 0.001, respectively) versus PLA. F2-isoprostanes, nitrite, and AA were increased after exercise (p = 0.004, p = 0.001, and p = 0.003, respectively), but the pattern of change was not different between treatments. This study indicates that plasma markers of exercise-induced oxidative stress were not affected by below-normal physiological concentrations of urate and a diminished antioxidant capacity within the plasma compartment.