Metal Toxicity and Speciation: A Review

Abstract

Background : Essential metal ions play a specific and fundamental role in human metabolism. Their homeostasis is finely tuned and any concentration imbalance in form of deficiency or excess could lead to a progressive reduction and failure of normal biological function, to severe physiological and clinical outcomes till death. Conversely, non-essential metals are not necessary for life and only noxious effects could arise after their exposure. Large environmental amounts of such chemicals come from both natural and anthropogenic sources, with the latter being predominant because of human activities. The dissipation of toxic metals contaminates water, air, soil, and food, causing a series of chronic and acute syndromes. Objective : This review discusses the toxicity of non-essential metals considering their peculiar chemical characteristics such as different forms, hard-soft character, oxidation states, binding capabilities and solubility, which can influence their speciation in biological systems, and subsequently, the main cellular targets. Particular focus is given to selected toxic metals, major non-essential metals or semimetals related to toxicity such as mercury, lead, cadmium, chromium, nickel and arsenic. In addition, we provide indications on the possible treatments/interventions on metal poisoning based on chelation therapy. Conclusion: Toxic metal ions can exert their peculiar harmful effects in several ways. They strongly coordinate to important biological molecules on the basis of their chemical-physical characteristics (manly HSAB properties) or replace essential metal ions from their natural locations in proteins, enzymes or in hard structures such as bones or teeth. Metals with redox properties could be key inducers of reactive oxygen species, leading to oxidative stress and cellular damage. Therapeutic detoxification, through complexation of toxic metal ions by specific chelating agents, appears an efficacious clinical strategy mainly in acute cases of metal intoxication.

Transmembrane Chloride Transport by Diphosphine‐Pd(II) Complexes: Effect of the Ligand Geometry

“…However, to broaden the scope of the work and to prove that the concept of using diphosphine metal complexes as anion carriers is not limited to Pd(II) complexes but it is valid in general for other transition metals we investigated the transport ability of the dppe complexes with Ni(II) and Cu(I). These metal ions were chosen because they form stable complexes with diphosphine ligands, although their toxicity, in particular of Ni(II) complexes, [30] will be a limitation to possible biological applications. Figure 8 reports a comparison of the activity of the three complexes in the HPTS assay.…”

Natural Dietary Compounds in the Treatment of Arsenic Toxicity

“…The specific synthesized antagonist As-chelating agent can restore the PHD activity; British Anti-Lewisite (BAL) competes with protein thiol groups for As binding. Once complexed, complexed is then excreted in the urine [ 44 ].…”

Chelation Combination—A Strategy to Mitigate the Neurotoxicity of Manganese, Iron, and Copper?

“…The affinity between the chelating agent and the toxic metal ion are the main qualities to take into account in chelation research and chelation therapy [ 25 , 26 , 27 ], in addition to the solubility of the chelating agent and of the formed metal chelate, both in water and in lipids [ 28 ]. Water solubility enables extracellular distribution and facilitates a fast urinary excretion, while a lipophilic chelating agent displays a higher penetration across cellular membranes, as well as across the barriers within and around the central nervous system (CNS) [ 1 ].…”