Investigating the effect of the heavy metals cadmium, lead and chromium alone and in combination on the components of the coagulation system

Abstract

In recent years, heavy metal exposure has become a serious concern for the health care sector as more humans are being exposed to heavy metals each day. Most of the environmental contamination and human exposure result from anthropogenic activities such as mining and smelting. The industrial and agricultural sectors also play a big role. Cigarette smoke in particular contains trace amounts of heavy metals that puts chronic smokers at serious risk. Previous studies have determined that there is a strong correlation between heavy metal exposure and the production of reactive oxygen species and nitric oxide formation. Therefore, the aim of this study was to investigate the effect of cadmium (Cd), lead (Pb) and chromium (Cr) alone and in combination on the erythrocytes and fibrin networks of the coagulation system in human blood. In addition, the ability of these metals to produce reactive oxygen species and nitrite were also determined. The choice of metals for this study were based on a previous study that compared the levels of metals between smokers and nonsmokers and found significantly higher levels of Cd, Pb and Cr in the platelet rich fibrin of smoking individuals. Whole blood was collected from ten volunteers (non-smokers) and exposed to x1, x10 and x100 the heavy metal concentration found in platelet-rich fibrin of cigarette smokers. The scanning electron microscopy analysis revealed that the Cd + Cr combination groups caused the highest degree of echinocyte formation and fibrin network alterations. These findings were supported by the thromboelastography® analysis that indicated a significant decrease in R-time and SP-values for the Cr-containing group, suggesting a shorter initiation time for clot formation. This may explain why considerable fibrin formation was observed in the Cr-exposed groups (alone or in combination) and support the fact that heavy metals have the ability to influence clot formation and increase the risk of thrombosis. The dichloro-dihydro-fluorescein diacetate (DCFH-DA) analysis revealed that the x10 Cd and Pb-exposed groups showed a considerable amount of reactive oxygen species production, compared to the other groups, which can potentially cause oxidative stress. No significant changes were observed in blood nitrite levels in any of the exposure groups. Therefore, the increased production of reactive oxygen species, altered red blood cell and fibrin network morphology as well as a decrease in some of the coagulation parameters support the hypothesis that the coagulation pathway is a potential target for heavy metal toxicity.