Mercury chloride toxicity in human erythrocytes: enhanced generation of ROS and RNS, hemoglobin oxidation, impaired antioxidant power, and inhibition of plasma membrane redox system

Abstract

Mercury is among the most toxic heavy metals and a widespread environmental pollutant. Mercury chloride (HgCl₂) is an inorganic compound of mercury which is easily absorbed in the gastrointestinal tract and then enters the blood where it can interact with erythrocytes. In this study, the effect of HgCl₂ on human erythrocytes was studied under in vitro conditions. Erythrocytes were treated with different concentrations of HgCl₂ (1-100 μM) for 1 h at 37 °C. Cell lysates were prepared and assayed for several biochemical parameters. HgCl₂ treatment resulted in oxidation of ferrous iron of hemoglobin to ferric form giving methemoglobin which is inactive as an oxygen transporter. However, the activity of methemoglobin reductase was increased. Hemoglobin oxidation was accompanied by heme degradation and the release of free iron. Protein oxidation was greatly increased with a simultaneous decrease in free amino and sulfhydryl groups and glutathione content. The antioxidant power of HgCl₂-treated erythrocytes was impaired resulting in lowered metal reducing and free radical quenching ability of these cells. This suggests that HgCl₂ induces oxidative stress in human erythrocytes. This was confirmed when superoxide anion, hydrogen peroxide, peroxynitrite, and nitric oxide generation were found to be dose-dependently increased in HgCl₂-treated erythrocytes. Glycolysis and pentose phosphate pathway, the two major pathways of glucose metabolism in erythrocytes, were also inhibited. HgCl₂ treatment also inhibited the plasma membrane redox system while the activities of AMP deaminase and glyoxalase-I were increased. These results show that HgCl₂ induces oxidative and nitrosative stress, oxidizes hemoglobin, impairs the antioxidant defense mechanism, and alters metabolic pathways in human erythrocytes.

Keywords: Antioxidant power; Erythrocytes; Hemoglobin; Mercury chloride; Methemoglobin; Reactive oxygen species.