Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

Abstract

Background/Aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the first to be affected following exposure and adverse effects on blood coagulation can lead to associated thrombotic disease. Although the plasma levels and the effects of cadmium (Cd) and chromium (Cr) on erythrocytes and lymphocytes have been described, the environmental exposure to heavy metals are not limited to a single metal and often involves metal mixtures, with each metal having different rates of absorption, different cellular, tissue, and organ targets. Therefore the aim of this study is to investigate the effects of the heavy metals Cd and Cr alone and whether Cr synergistically increases the effect of Cd on physiological important processes such as blood coagulation. Methods: Human blood was exposed to the heavy metals ex vivo, and thereafter morphological analysis was performed with scanning electron- and confocal laser scanning microscopy (CLSM) in conjunction with thromboelastography®. Results: The erythrocytes, platelets and fibrin networks presented with ultrastructural changes, including varied erythrocytes morphologies, activated platelets and significantly thicker fibrin fibres in the metal-exposed groups. CLSM analysis revealed the presence of phosphatidylserine on the outer surface of the membranes of the spherocytic erythrocytes exposed to Cd and Cr alone and in combination. The viscoelastic analysis revealed only a trend that indicates that clots that will form after heavy metal exposure, will likely be fragile and unstable especially for Cd and Cr in combination. Conclusion: This study identified the blood as an important target system of Cd and Cr toxicity.

Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: An ex vivo study

“…The relevance of using an ex vivo blood model is that in previous studies, it was found that metals such as Cd, Cr and Hg compromise rat blood vessel wall integrity, rat blood haemostasis and human blood haemostasis, which indicate that these effects can increase the risk for thrombosis and CVDs. 18,19 In a novel approach, in this study, heavy metal concentrations based on the WHO limit for drinking water were evaluated. These levels are physiologically relevant and results can provide information on the robustness of established limits, that is, levels should be reduced.…”

“…17 The cellular and tissue effects of each metal, usually alone but increasingly as part of mixtures, have been researched using animal models. 18,19 Although these studies provide valuable information on specific tissue and cellular targets, the information on the effects on human tissue are limited.…”

“…At these concentrations, blood markers of tissue damage were not increased, but extensive tissue and cellular damage occurred, which included damage to blood vessels and altered blood haemostasis and indicates that exposure to these metals may lead to the development of CVD in humans. 18,19 The aim of this study was to determine the oxidative potential of Cu, Mn and Hg as well as the effect of these metals at the WHO safety limit on the ultrastructure and viscoelastic properties of blood using an ex vivo blood model.…”

Effect of Chromium on Glutathione-S-Transferase and Catalase Activity and their Respective Gene Expressions in the Brain Tissue of F1 Generation Mice Following Prenatal Exposure: Modulation by Quercetin

“…Lower levels occur in rural areas and higher levels occur in large urban centres. Majority of specimens submitted for analysis from unexposed individual contain 0.3 µg/mL to 0.9 µg/mL [11][12][13][14]. Moreover studies have shown that Cr compounds are essential micronutrients having important physiological functions and are also considered to improve glucose tolerance in patients suffering from diabetes [15,16].…”

Effect of diamond-like carbon doped with chromium on cell differentiation, immune activation and apoptosis

“…In addition, doping the DLC coating with F can decrease the platelet covered area (Hasebe et al, 2007, additional reference). The potential influence of Cr on platelet and leukocyte adhesion and activation, thrombin generation and fibrin formation has been reported in several studies (Gossart et al, 2019, Venter et al, 2017, Ollivier et al, 2016. Specifically, blood exposed to Cr, under ex vivo conditions, can exhibit varied erythrocyte morphologies, activated platelets and thicker fibrin fibres than in a control group (Venter et al, 2017, additional reference).…”