Erythrocytes as a Model for Heavy Metal-Related Vascular Dysfunction: The Protective Effect of Dietary Components

Abstract

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.

Olive Oil Phenols Prevent Mercury-Induced Phosphatidylserine Exposure and Morphological Changes in Human Erythrocytes Regardless of Their Different Scavenging Activity

“…Interestingly in this respect, RBC have been proposed as a potential link between diabetes and Alzheimer’s diseases [ 51 ]. Finally, we recently reviewed data indicating the rationale for using of RBC as a model for heavy metal-induced endothelial dysfunction, including Hg [ 35 ]. In this respect, a link between this highly toxic environmental pollutant and CVD has been proposed, and several authors indicate that Hg human exposure may act as a potential risk factor for these pathologies [ 52 , 53 ].…”

“…Interestingly, beside the well-known neuro and nephro toxic effects, this highly toxic wide-spread pollutant [ 32 ] can significantly affect cardiovascular health [ 33 , 34 ]. RBC have been proposed as contributing to endothelial dysfunction and thrombotic events [ 35 ].…”

“…Intact human RBC have been subjected in vitro to treatment with mercuric chloride (HgCl 2 ) or Ca 2+ -ionophore. It is well known, indeed, that alterations in calcium homeostasis are associated with Hg toxicity, and increased intracellular Ca 2+ induces PS exposure [ 35 ]. The protective effect of the selected phenols and the underlying mechanism(s) were evaluated by measuring several hallmarks including PS exposure, reactive oxygen species (ROS) generation, GSH depletion and MVs formation.…”

Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids

“…Among the variety of dietary flavonoids, the beneficial role of chrysin (CR), which is found mainly in passion fruit, honey, and propolis in preventing Hg-induced alterations in both human erythrocytes and neuroblastoma cells has been investigated [189]. Finally, a number of investigations have revealed the role of olive oil polyphenols in preventing Hg toxicity [190].…”

Effect of Mercury on Membrane Proteins, Anionic Transport and Cell Morphology in Human Erythrocytes

“…In this respect, workers occupationally exposed to Hg vapor show increased blood concentration of this heavy metal, associated with significant alterations in the coagulation system [14]. Accordingly, Hg intoxication is associated with an increased risk of cardiovascular diseases (CVD) [15][16][17].…”