Attenuation of Hg(II)-induced cellular and DNA damage in human blood cells by uric acid

Abstract

Mercury (Hg) is a widespread environmental pollutant and toxicant which induces multiple organ damage in humans and animals. Hg toxicity is mediated by the induction of oxidative stress in target cells. We have used uric acid (UA), a potent antioxidant found in biological fluids, to protect human red blood cells (RBC) and lymphocytes against Hg-mediated cell, organelle and genotoxicity. RBC were incubated with HgCl2, an Hg(II) compound, either alone or in presence of UA. Incubation of RBC with only HgCl2 increased production of nitrogen and oxygen radical species, enhanced methemoglobin levels, heme degradation, free ferrous iron, oxidation of proteins and membrane lipids and reduced antioxidant capacity of cells. UA enhanced the antioxidant capacity of RBC and restored metabolic, plasma membrane-bound and antioxidant enzyme activities. Scanning electron microscopy showed that UA prevented HgCl2-mediated morphological changes in RBC. HgCl2 dissipated the mitochondrial membrane potential and increased lysosomal membrane damage in lymphocytes, but UA pre-treatment attenuated these effects. Genotoxicity analysis by comet assay showed that UA protected lymphocyte DNA from HgCl2-induced damage. Importantly, UA itself did not exhibit any deleterious effects in either RBC or lymphocytes. Thus, UA protects human blood cells from Hg(II)-mediated oxidative damage reducing the harmful effects of this extremely toxic metal. We suggest that UA performs a similar protective role in the plasma against heavy metal toxicity.