Metal Toxicity and Speciation: A Review


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.

Authors: Massimiliano Peana, Alessio Pelucelli, Serenella Medici, Rosita Cappai, Valeria Marina Nurchi, Maria Antonietta Zoroddu
; Full Source: Current medicinal chemistry 2021 Mar 24. doi: 10.2174/0929867328666210324161205.