Prooxidant effect of uric acid on human leukocytic DNA: An in vitro and ex vivo study

Uric acid is a major contributor to the total antioxidant capacity of human plasma. However, this endogenous substance's antioxidant and prooxidant properties have not yet been reported.

In this study, the comet assay was employed in vitro to determine the effect of uric acid on DNA damage in human lymphocytes and leukocytic DNA damage in hyperuricemia patients with and without renal failure.

DNA damage in lymphocytes occurred at uric acid concentrations of ≥600 μM. Adding catalase to the uric acid solution diminished the damaging effect, indicating that hydrogen peroxide mediated the prooxidant activity. Moreover, adding Fe²⁺ did not enhance the DNA damage, suggesting that the urate's prooxidant activity is independent of the Fenton reaction. The unstable nature of uric acid at nearly neutral and acidic pH levels resulted in autooxidation and the generation of hydrogen peroxide. Maintaining the stability of uric acid in vivo may lead to the consumption of antioxidants in the body and affect the antioxidant status. Hyperuricemia patients with and without renal failure had higher levels of leukocytic DNA damage compared to healthy individuals. However, there was no significant difference in leukocytic DNA damage between hyperuricemia patients with and without renal failure, which showed that the damaging effect was not due to renal failure. A correlation study suggested that serum uric acid level had a stronger correlation with DNA damage than the severity of renal failure as indicated by serum creatinine or urea.

Uric acid demonstrated prooxidant activity in both in vitro and in vivo studies, which was mediated by the production of hydrogen peroxide and independent of both the Fenton reaction and renal failure.