Water contamination with metals due to anthropogenic activity is increasing and subsequent exposure increases the risk of associated toxicity. Exposure is not limited to a single metal but usually ...involves mixtures of different metals at different concentrations. Little is known about the contribution of this type of exposure, in humans, to the development of non-communicable diseases such as cardiovascular disease, and an increased risk to thrombosis. The World Health Organization has established limits for metal levels in drinking water and this includes levels for copper (Cu), manganese (Mn) and mercury (Hg). In this study, at 100X these limits, the ability of the metals’ oxidative effects as catalysts of the Fenton reaction and/or ability to bind glutathione (GSH) were determined. The haemostatic effects of these metals, alone and in combination, at the World Health Organization limit were then evaluated. The ultrastructural and viscoelastic alterations of exposed ex vivo whole blood were also evaluated using scanning electron microscopy and thromboelastography® (TEG), respectively. Cu, alone and in combination with Mn and/or Hg, induced hydroxyl radical formation and reduced GSH levels. Ex vivo exposure caused deformation of erythrocytes and accelerated platelet activation especially for Cu, alone and in combination, with Mn. Reduction in the lysis potential of the clot was also observed for all combinations, especially Cu in combination with Hg as well as Mn alone. Although the TEG findings were not statistically significant, the trends indicate that the exposure to these metals, alone and in combination, adversely affects thrombus formation in ex vivo blood, thereby potentially increasing the risk in exposed individuals for thrombosis.
The distribution of metals across the environment is increasingly becoming a major concern as they not only pollute the environment but also pose a danger to humans and animals. Human exposure to ...heavy metals often occurs as a combination of metals the synergistic effects of which can be more toxic than a single metal. The aim of this study was to investigate the effects that the metals mercury (Hg), nickel (Ni) and manganese (Mn) alone and in combination have on erythrocyte morphology and other components of the coagulation system using the haemolysis assay, scanning electron microscopy (SEM), and confocal laser scanning microscopy. Human blood was exposed to the heavy metals ex vivo, and percentage haemolysis was determined. Ultrastructural analysis of erythrocytes, platelets and fibrin networks was performed using SEM. Analysis of phosphatidylserine (PS) flip-flop was determined using confocal laser scanning microscopy. At the highest concentration of 10,000× the World Health Organization safety limit, all the metals caused haemolysis. The results showed that the exposure of erythrocytes to Hg alone and in combination with other metals displayed more haemolysis compared to Ni and Mn alone and in combination. Components of the coagulation system showed ultrastructural changes, including the formation of echinocytes and the activation of platelets with all single metals as well as the combinations. Confocal laser scanning microscopy analysis showed the presence of PS on the outer surface of the echinocytes that were exposed to metals alone and in combination. It can, therefore, be concluded that these heavy metals have a negative impact on erythrocytes and the coagulation system.
