Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

TLDR

Improved protection against oxygen radicals during primate evolution may have extended lifespan and reduced cancer, and uric acid—an antioxidant that scavenges singlet oxygen and radicals—has been implicated in this protective effect. The authors propose that plasma uric acid, whose levels rose during primate evolution due to mutations, serves as one of these protective systems. At physiological concentrations, urate reduces oxo‑heme oxidants, protects erythrocytes from lipid peroxidation and lysis, is as effective as ascorbate, and, with plasma levels around 300 µM, constitutes a major antioxidant in humans.

Abstract

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.