Urate hydroperoxide: A new reported oxidant generated in inflammatory conditions

Uric acid is the final product of purine metabolism in humans and is an alternative substrate for myeloperoxidase. The oxidation of uric acid by this enzyme generates urate free radical and urate hydroperoxide. This study investigated the formation of urate hydroperoxide in inflammatory cells and how it alters the redox balance in these cells. Human leukemic cells (HL-60) were differentiated in neutrophils (dHL-60) and blood peripheral neutrophils were isolated from healthy donors. Cells were activated with phorbol myristate acetate in presence or absence of uric acid. Oxygen consumption and superoxide production were increased by 7 and 89% in presence of uric acid. Both dHL-60 cells and blood neutrophils efficiently oxidized uric acid to urate hydroperoxide. This oxidation was dependent on myeloperoxidase activity and superoxide production. Uric acid decreased HOCl likely by the competition between chloride and uric acid by myeloperoxidase catalysis. Incubation with uric acid decreased GSH/GSSG ratio and increased peroxiredoxin oxidation. In spite of being considered the main antioxidant in plasma, uric acid can be oxidized in inflammatory conditions leading to an oxidative environment and contribute to tissue damage in inflammation.