Neurotoxicity of Metal Mixtures

Abstract

Metals are the oldest toxins known to humans. Metals differ from other toxic substances in that they are neither created nor destroyed by humans (Casarett and Doull's, Toxicology: the basic science of poisons, 8th edn. McGraw-Hill, London, 2013). Metals are of great importance in our daily life and their frequent use makes their omnipresence and a constant source of human exposure. Metals such as arsenic [As], lead [Pb], mercury [Hg], aluminum [Al] and cadmium [Cd] do not have any specific role in an organism and can be toxic even at low levels. The Substance Priority List of Agency for Toxic Substances and Disease Registry (ATSDR) ranked substances based on a combination of their frequency, toxicity, and potential for human exposure. In this list, As, Pb, Hg, and Cd occupy the first, second, third, and seventh positions, respectively (ATSDR, Priority list of hazardous substances. U.S. Department of Health and Human Services, Public Health Service, Atlanta, 2016). Besides existing individually, these metals are also (or mainly) found as mixtures in various parts of the ecosystem (Cobbina SJ, Chen Y, Zhou Z, Wub X, Feng W, Wang W, Mao G, Xu H, Zhang Z, Wua X, Yang L, Chemosphere 132:79-86, 2015). Interactions among components of a mixture may change toxicokinetics and toxicodynamics (Spurgeon DJ, Jones OAH, Dorne J-L, Svendsen C, Swain S, Stürzenbaum SR, Sci Total Environ 408:3725-3734, 2010) and may result in greater (synergistic) toxicity (Lister LJ, Svendsen C, Wright J, Hooper HL, Spurgeon DJ, Environ Int 37:663-670, 2011). This is particularly worrisome when the components of the mixture individually attack the same organs. On the other hand, metals such as manganese [Mn], iron [Fe], copper [Cu], and zinc [Zn] are essential metals, and their presence in the body below or above homeostatic levels can also lead to disease states (Annangi B, Bonassi S, Marcos R, Hernández A, Mutat Res 770(Pt A):140-161, 2016). Pb, As, Cd, and Hg can induce Fe, Cu, and Zn dyshomeostasis, potentially triggering neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Additionally, changes in heme synthesis have been associated with neurodegeneration, supported by evidence that a decline in heme levels might explain the age-associated loss of Fe homeostasis (Atamna H, Killile DK, Killile NB, Ames BN, Proc Natl Acad Sci U S A 99(23):14807-14812, 2002).The sources, disposition, transport to the brain, mechanisms of toxicity, and effects in the central nervous system (CNS) and in the hematopoietic system of each one of these metals will be described. More detailed information on Pb, Mn, Al, Hg, Cu, and Zn is available in other chapters. A major focus of the chapter will be on Pb toxicity and its interaction with other metals.

Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts

“…Cadmium administration caused depressogenic, anxiogenic and memory impairing effects. It has been shown that the toxic effect of cadmium on the CNS is due to an increase in permeability of the BBB, which enhances the penetration and accumulation of cadmium in brain (Andrade et al, 2017). Cadmium exerts its neurotoxic effects by blocking Ca ++ -dependent intracellular signaling pathways and inhibiting the fusion of storage vesicles, resulting in decreased neurotransmitter at the synapse (Wang and Du, 2013).…”

“…Heavy metals, such as mercury, lead and cadmium, are widely distributed in nature; however, they have no nutritional importance. Cadmium is an extensively distributed toxicant because of its excessive use in modern lifestyles (Andrade et al, 2017). For example, this heavy metal is used in the manufacture of household appliances, batteries and paints.…”

“…The toxic effect of cadmium is due to its long half-life, causing its accumulation in living tissues for long periods of time. Cadmium is also regarded as a neurotoxicant as it can easily cross the blood brain barrier (BBB) and impairs neuronal functions (Andrade et al, 2017), including changes in neurotransmitter synthesis, release and synaptic activity. Cadmium exposure has also been shown to alter the activity of acetylcholinesterase and sodium-potassium ATPase in various rat brain regions including cortex, hippocampus, cerebellum, striatum and hypothalamus (Wang et al, 2018).…”

Wholegrains and health: Many benefits but do contaminants pose any risk?

“…structural proteins, enzymes and nucleic acids) disrupting their function (Andrade et al . ; Kosek‐Hoehne et al . ).…”

Evaluation of Lead and Copper content in hair of workers from oil product distribution companies in Iraq

“…But due to wide spread occurrence of copper this increases chances of overexposure leading to neurotic symptoms like affective disorder (Ashish, Neeti, Himanshu, 2013;Nastoulis et al, 2017). Both copper and lead are harmful in highly exposed individuals, but copper is much less toxic, it has been shown that elevated levels of copper for 14 days or more can cause nausea, vomiting, diarrhea and permanent organs damage (Andrade, Aschner, Marreilha, 2017).…”